Iaoe?iiaeueia aeaaeai?y iaoe oe?a?ie

?inoeooo o?c?ieia?? ?i. I.I. aiaiiieueoey

AEiein Ieaenaiae? A?eoi?iae/

OAeE 577.352.5:577.353

Iaia?aii? oa aioo??oiueiee?oeii? iaoai?cie I-oie?ia?a?/ii? aeoeaaoe??
aeaaeaiueeii’yciaeo ee?oei oiieiai eeoa/ieeo

03.00.02 — A?io?ceea

Aaoi?aoa?ao

aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

aeieoi?a a?ieia?/ieo iaoe

Ee?a — 1999

Aeena?oaoe??th ? ?oeiien

?iaioa aeeiiaia a ?inoeooo? o?c?ieia?? ?i. I.I. Aiaiiieueoey
Iaoe?iiaeueii? Aeaaeai?? iaoe Oe?a?ie

Iaoeiaee eiinoeueoaio: aeaaeai?e IAI
Oe?a?ie, aeieoi? iaaee/ieo iaoe

i?ioani? Ooaa I.O.

caa?aeoth/ee a?aeae?eii ia?aiai-i’yciai? o?c?ieia??

?inoeoooo o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie

Io?oe?ei? iiiiaioe: aeieoi?
a?ieia?/ieo iaoe, i?ioani? Ceia A.E.

i?ioani? eaoaae?e a?io?ceee

Ee?anueeiai oi?aa?neoaoo ?i. Oa?ana Oaa/aiea

aeieoi? a?ieia?/ieo iaoe Eiiiiaiei I. ?.

i?ia?aeiee iaoeiaee ni?a?ia?oiee a?aeae?eo caaaeueii? o?c?ieia??
ia?aiai? nenoaie ?inoeoooo o?c?ieia??

?i. I.I. Aiaiiieueoey IAI Oe?a?ie

aeieoi? a?ieia?/ieo iaoe Aanaeianueeee I. N.

canooiiee aee?aeoi?a I?aeia?iaeiiai Oeaio?o

Iieaeoey?ii-o?c?ieia?/ieo aeine?aeaeaiue

I?ia?aeia onoaiiaa: ?inoeooo a?io?i?? ?i. I.A. Iaeeaae?ia
Iaoe?iiaeueii? Aeaaeai?? iaoe Oe?a?ie, a?aeae?e a?io?i?? i’yc?a, i.
Ee?a.

Caoeno a?aeaoaeaoueny 7 aa?aciy 2000 ?. i 10 aiaeei? ia can?aeaii?
niaoe?ae?ciaaii? a/aii? ?aaee Ae01.13.01 i?e ?inoeooo? o?c?ieia?? ?i.
I.I. Aiaiiieueoey Iaoe?iiaeueii? Aeaaeai?? iaoe Oe?a?ie ca aae?anith:
252 024, i. Ee?a, aoe. Aiaiiieueoey, 4.

C aeena?oaoe??th iiaeia iciaeiieoeny o a?ae?ioaoe? ?inoeooo? o?c?ieia??
?i. I.I. Aiaiiieueoey Iaoe?iiaeueii? Aeaaeai?? iaoe Oe?a?ie ca
aae?anith: 252 024, i. Ee?a, aoe. Aiaiiieueoey, 4.

Aaoi?aoa?ao ?ic?neaiee 6 n?/iy 2000 ?.

A/aiee nae?aoa? niaoe?ae?ciaaii? a/aii? ?aaee

aeieoi? a?ieia?/ieo iaoe
Ni?ie?ia-Ia??ia C.I.

32

Caaaeueia oa?aeoa?enoeea ?iaioe

Aeooaeuei?noue i?iaeaie

Iaoai?cie ?aaoeyoe?? oiiono oa nei?i/aiiy aeaaeaiueeeo iyc?a
aaaaoaoeaiith ia?aiaith nenoaiith ? oeaio?aeueieie i?iaeaiaie
o?c?ieia??, oa?iaeieia?? ? a?io?ceee aeaaeaiueeeo iyc?a. Aoeaoeeoie?i,
i?eioeeiiaee iaae?aoi? ia?aneiiaoe/ii? ia?aiai? nenoaie, aeeeeea?
caoaeaeaiiy ? nei?i/aiiy a?noea?aeueieo aeaaeaiueeeo iyc?a, a oaeiae
aeayeeo noaeei. Oaeei /eiii, aac aeaoaeueiiai aeine?aeaeaiiy iaoai?ci?a
ae?? aoeaoeeoie?io ia aeaaeaiueeii’ycia? ee?oeie (AIE) iaiiaeeeaa
?icoi?iiy ooieoe?e ??cieo i?aai?a, ii?ooaiue iioi?eee i?e ??ciiiai?oieo
caoai?thaaiiyo oa iiooe iiaeo i?aeoiae?a o e?eoaaii? ?iceaae?a
aeeoaeueieo oeyo?a, oeoieiai-eeoeiaiai oa na/iaeae?eueiiai o?aeo?a.

Caoaeaeoth/a ae?y aoeaoeeoie?io oa ?ioeo oie?ia?a?/ieo aaii?no?a
(iai?eeeaae, ea?aaoie?io) iaoiiaeaia aeoeaaoe??th ionea?eiiaeo
?aoeaioi??a. Inoaii? iaeaaeaoue aei aaeeei? ?iaeeie ?aoeaioi??a, ui
ae?thoue ia aoaeoi?e — ?iii? eaiaee oa aiceie — oeyoii aeoeaaoe??
AOO-ca’ycoth/eo Ga?ee?a.

Oeaio?aeueiith niieo/iith eaieith i?ae aeoeaaoe??th ionea?eiiaeo
?aoeaioi??a oa i’yciaei nei?i/aiiyi ? i?aeaeuaiiy ??aiy
aioo??oiueiee?oeiiiai eaeueoe?th, a iniiaieie i?ioeanaie — ao?ae Ca2+ a
ee?oeio i?e oie?ia?a?/i?e aeaiiey?ecaoe?? iaia?aie oa aea?eueiaiiy Ca2+
?c aioo??oiueiee?oeiieo aeaii. I?eeiath/e aei oaaae aaoa?iaaii?noue
ionea?eiiaeo ?aoeaioi??a ? niaoeeo?/i?noue eiaeiiai ?c i?aeoei?a a
aeoeaaoe?? oeo /e ?ioeo G-a?ee?a ?, oaeei /eiii, o caioneo aai ae
?aaoeyoe?? ??ciiiai?oieo ?aaeoe?e, ia no/aniiio aoai? noaiiaeoueny ana
a?eueo i/aaeaeiei, ui oie?ia?a?/iee eiio?ieue aeaaeaiueeeo i’yc?a
iaiiaeeeai c?icoi?oe ye i?inoo noio ?cieueiaaieo iiae?e. Aeooaeueiei ?
aea/aiiy ??ciiiai?oieo aca?iiae?e o oe?e neeaaei?e nenoai?, ?ie? ??cieo
i?aeoei?a ionea?eiiaeo ?aoeaioi??a, iaoai?ci?a Ca2+- oa
InsP3-?iaeoeiaaiiai aea?eueiaiiy Ca2+, a oaeiae iaia?aiieo iaoai?ci?a
Ioie?ia?a?/iiai caoaeaeaiiy AIE.

Iaoai?ciai aeaiiey?ecoth/i? ae?? aoeaoeeoie?io o aeai?e ?iaio? aoei
i?eae?eaii iniaeeao oaaao, ine?eueee iaia?aii? iiae??, ui i?eaiaeyoue
aei ?? aeaiiey?ecaoe??, ? ia?oeie ? iaeiaio aeine?aeaeaieie o neeaaeiiio
eaioethaeeo ?aaeoe?e, ui aeieeathoue i?e aeoeaaoe?? oie?ii?aoeaioi??a.

Ca’ycie ?iaioe c iaoeiaeie i?ia?aiaie, ieaiaie, oaiaie

?iaioo aeeiiaii o ?aieao iaoeiaeo i?ia?ai a?aeae?eo ia?aiai-i’yciai?
o?c?ieia?? ?inoeoooo o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie:
«C’ynoaaiiy iieaeoey?ieo iaoai?ci?a niaoeeo?/ieo ci?i i?ia?aeiino?
ee?oeiieo iaia?ai i?e aeieeiaii? iniiaieo ia?aiaeo i?ioean?a»,
«Iaoai?cie aeaeo?i- ? oaiiea?iaaii? eaeueoe??ai? i?ia?aeiino? iaia?aie
oa ?? ?ieue o ni?yaeaii? caoaeaeaiiy-nei?i/aiiy o aeaaeaiueeeo iycao»,
«Iaoai?cie iaoaaie?/ii? ?aaoeyoe?? ?iiieo eaiae?a ? nei?i/aiiy
aeaaeaiueeii’yciaeo ee?oei».

Iaoa aeine?aeaeaiiy

Iaoa ?iaioe iieyaaea o aea/aii? iaia?aiieo oa aioo??oiueiee?oeiieo
iaoai?ci?a Ioie?ia?a?/ii? aeoeaaoe?? aeaaeaiueeii’yciaeo ee?oei oiieiai
eeoa/ieeo.

Caaea/? aeine?aeaeaiiy

1. Aeine?aeeoe a?io?ce/i? ? oa?iaeieia?/i? aeanoeaino?
iioaioe?aeea?iaaieo ?iiieo eaiae?a iaia?aie iae?ii?a i?aei’yciaiai
ieaoeaa oa AIE oiieiai eeoa/ieeo.

2. Aeine?aeeoe ?ieue ? iaoai?cie Ca2+ ? InsP3-?iaeoeiaaiiai
aea?eueiaiiy Ca2+ o AIE, cie?aia ?ieue iioaioe?aeea?iaaiiai aoiaeo Ca2+
a aeoeaaoe?? Ca2+?iaeoeiaaiiai ? iiaeoeyoe?? InsP3?iaeoeiaaiiai
aea?eueiaiiy Ca2+.

3. Aeine?aeeoe iaoai?cie aeaiiey?ecoth/i? ae?? ionea?eiiaeo aaii?no?a
ia iaia?aio ?cieueiaaieo AIE ileum ii?nueei? naeiee.

4. Aeine?aeeoe ?ieue aeoeaiaaieo G-a?ee?a a ?aaoeyoe?? eao?iiii?
i?ia?aeiino? iaia?aie AIE ? ?ic?iaeoe e?euee?ni? iiaeae?, ye? a
iienoaaee e?iaoeeo eao?iiiiai no?oio, aeieeath/iai i?e aeoeaaoe??
ionea?eiiaeo oie?ii?aoeaioi??a.

5. Aeine?aeeoe iaoai?cie oie?ia?a?/ii? ?aaoeyoe?? iioaioe?aecaeaaeieo
Ca2+ eaiae?a Loeio iaia?aie AIE oiieiai eeoa/ieeo.

Iaoeiaa iiaecia io?eiaieo ?acoeueoao?a

1. Iieacaia iayai?noue ?aaaia?aoeaiiai Ca2+?iaeoeiaaiiai aea?eueiaiiy
Ca2+ o a?noea?aeueieo AIE, ui aeoeao?oueny iaa?oue i?e iacia/iiio aoiae?
Ca2+ /a?ac L-oei Ca2+ eaiae?a.

2. Iieacaii, ui i?e i?aeaeuaii? aioo??oiueiee?oeiii? eiioeaio?aoe??
?ii?a Ca2+ a?aeaoaa?oueny ii/aoeiaa iineeaiiy oa cao?eiaia i?eai?/aiiy
InsP3-?iaeoeiaaiiai aea?eueiaiiy Ca2+ ye i?e aeoeaaoe?? ionea?eiiaeo
oie?ii?aoeaioi??a, oae ? i?e ae?? aeciaaiiiai InsP3.

3. Aecia/aia ?ieue G-a?ee?a o iiaeoeyoe?? iioaioe?aecaeaaeiino?
eao?iiii? i?ia?aeiino? ye i?eioeeiiaiai iaoai?cio ?aaoeyoe?? eao?iiieo
eaiae?a, ye? a?aee?eaathoueny i?e aeoeaaoe?? ionea?eiiaeo
oie?ii?aoeaioi??a.

4. Aeine?aeaeai? aeanoeaino? iiiaeeiieeo eao?iiieo eaiae?a, a oaeiae
iiaeoethth/ee aieea aeaiaaeaioieo eao?ii?a ? i?ioii?a ia eao?iiio
i?ia?aei?noue.

5. Iieacai? i?eioeeiiaa ?ieue I2 ?aoeaioi??a ? iiaeoethth/a ?ieue I3
?aoeaioi??a a aeoeaaoe?? eao?iiieo eaiae?a. Aia?oa aecia/aia i?yia ?ieue
I2 i?aeoeio ionea?eiiaeo ?aoeaioi??a o aeaaeaiueeeo iycao.

6. Anoaiiaeaii iiaee iaoai?ci aeanaineoecaoe?? eao?iiieo eaiae?a, ui
iieyaa? a ciaioaii? aeoeaaoe?? G-a?ee?a o i?ioean? a?ae?ie?co oa
ae/a?iaiiy AOO.

7. Aeine?aeaeaia ?ieue G-a?ee?a o ea?aaoie?icaeaaei?e iiaeoeyoe?? Ca2+
no?oio ? aeaia ii??aiyeueia oa?aeoa?enoeea aeoeaaoe?? eao?iiiiai no?oio
? i?eai?/aiiy Ca2+ no?oio.

I?aeoe/ia cia/aiiy io?eiaieo ?acoeueoao?a

Aeaia ?iaioa iineoue a iniiaiiio oai?aoe/iee oa?aeoa? ? cia/ii
iiaeeaeth? ? ?icoe?th? no/ani? oyaeaiiy a?aeiinii iaoai?ci?a
aea?eueiaiiy Ca2+ o AIE ? aaia?aoe?? caoaeaeaiiy i?e aeoeaaoe??
ionea?eiiaeo ?aoeaioi??a. Cia/ei?noue io?eiaieo ?acoeueoao?a oeei ia
iaiaaeo?oueny, ine?eueee aeaiee oei iaia?aiieo ?aoeaioi??a iaeaaeeoue
aei aaeeeiai n?iaenoaa oae caaieo 7OI ?aoeaioi??a, ui ia?aoiao? aei
aeaio oeny/ i?aaenoaaiee?a. No?oeoo?a, iaoai?cie aeoeaaoe?? ? ia?aaea/?
neaiaeo aeey oeeo ?aoeaioi??a aaaaoi o /iio iiae?ai?, oiio ?o aecia/aiiy
aeey iaeiiai ?c i?aaenoaaiee?a ia? aaeeea caaaeueiia?ieia?/ia cia/aiiy.
I?i i?aeoe/io cia/ei?noue 7-OI ?aoeaioi??a na?ae/eoue oie oaeo, ui ae?y
aeecueei 60% e?e?a ni?yiiaaia naia ia oe? ?aoeaioi?e. Cie?aia,
aioaaii?noe ionea?eiiaeo ?aoeaioi??a canoiniaothoueny i?e e?eoaaii?
??cieo caoai?thaaiue, iaoiiaeaieo i?aeaeuaiith ?aaeoeai?noth ?
iioi?eeith aeaaeaiueeeo iyc?a (aeenooieoe?y eeoa/ieeo ? n?/iaiai i?oo?a,
iano?oeoe?y aeeoaeueieo oeyo?a, a?iio?aeueia anoia, iaioe/ia ae?acea, oa
?i.). Oaeei /eiii, aeine?aeaeaiiy iaoai?ci?a oie?ia?a?/iiai eiio?ieth
ae?yeueiino? aeaaeaiueeeo iyc?a noai?th? oai?aoe/io iniiao aeey
oe?eani?yiiaaiiai iiooeo naeaeoeaieo oa?iaeieia?/ieo i?aia?ao?a ? a?eueo
aoaeoeaii? ei?aeoe?? ??cieo iaoieia?/ieo noai?a.

Iniaenoee aianie caeiaoaa/a

Aaoi? naiino?eii ?ic?iaea iaoiaeeee io?eiaiiy iiiaeeiieeo AIE ? i?ia?a
ia?aaaaeio a?eueo?noue aenia?eiaio?a, ?o noaoenoe/io ia?iaeo, aiae?c ?
ocaaaeueiaiiy ?acoeueoao?a, a oaeiae aiooaaa aei ae?oeo iaoeia? noaoo?.
Aeaye? aenia?eiaioe aoei aeeiiaii ni?eueii c ?ioeie aeine?aeieeaie c
i?eaeecii iaeiaeiaei aianeii:

1. Aeine?aeaeaiiy ?iiieo no?oi?a o iaia?ai? AIE oiieiai eeoa/ieeo uo?a —
N.A. Ni??iia (?inoeooo o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie).

2. Aeine?aeaeaiiy ?iiieo no?oi?a o iaia?ai? iae?ii?a i?aei’yciaiai
ieaoeaa oiieiai eeoa/ieeo ii?nueei? naeiee — E.A. Aaeaeai (?inoeooo
o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie; Aea?aeaaiee oi?aa?neoao
ooaoo Iaaei, NOA).

3. Aeine?aeaeaiiy i?eai?/oth/i? ae?? Ca2+ ia InsP3-?iaeoeiaaia
aea?eueiaiiy Ca2+ — N. Eiii?? (Oi?aa?neoao A?oo, ssiii?y).

4. Aeine?aeaeaiiy ae?? ea?aaoie?io ia Ca2+ eaiaee AIE ileum ii?nueei?
naeiee — A. Iooeianueeee (?inoeooo aenia?eiaioaeueii? oa?iaeieia??
Aeaaeai?? iaoe Neiaa//eie).

Ai?iaaoe?y ?iaioe

Iniiai? iieiaeaiiy aeena?oaoe?? aoee i?aaenoaaeai? ia nai?ia?ao
?inoeoooo o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie (1988-1997),
a?aeae?eo oa?iaeieia?? ? ee?i?/ii? oa?iaeieia?? Iaaee/ii? oeiee
aini?oaeth Na. Aai?a?y (Eiiaeii) ? ?inoeoooo aenia?eiaioaeueii?
oa?iaeieia?? Aeaaeai?? iaoe Neiaa//eie (A?aoeneaaa), ia 5-io
I?aeia?iaeiiio neiiic?oi? “O?c?ieia?y ? oa?iaeieia?y aeaaeaiueeeo iyc?a“
(Aa?ia, 1988), ia Ananithcieo neiiic?oiao ”Iiiaeeiie? eaiaee o
a?ieia?/ieo iaia?aiao“ (Ioueii, 1989; Iineaa, 1990), ia OIII c?cae?
Oe?a?inueeiai O?c?ieia?/iiai oiaa?enoaa (Oa?e?a, 1990), ia
?aaeyinueei-?niainueeiio neiiic?oi? ii o?ceei-o?i?/i?e a?ieia?? (Ee?a,
1990), ia can?aeaiiyo FASEB (Aoeaioa, 1991; Ein Aiaeaean, 1992), ia
Eiioa?aioe?? ii caoai?thaaiiyo o?aaiiai o?aeoo (Iiaee I?eaai, 1991), ia
can?aeaii? Aia?eeainueei? Anioe?aoe?? aano?iaioa?ieia?a (Nai O?aioeenei,
1992), ia 2-io I?aeia?iaeiiio neiiic?oi? ii aca?iiae?? iicie — o?aaiee
o?aeo (Eaia?eaeae, 1992), ia OOOII I?aeia?iaeiiio O?c?ieia?/iiio
eiia?an? (Aeacai, 1993), ia o?ueio can?aeaiiyo O?c?ieia?/iiai oiaa?enoaa
Aaeeeia?eoai?? (Eaia?eaeae, 1994; Eiiaeii, 1996), ia 1io Eiia?an?
Oe?a?inueeiai a?io?ce/iiai oiaa?enoaa (Ee?a, 1994), ia ni?eueiiio
can?aeaii? O?c?ieia?/ieo oiaa?enoa ssiii??, Aaeeeia?eoai?? ? e?a?i
?a?iie (Iaaiy, 1995), ia can?aeaiiyo A?io?ce/iiai oiaa?enoaa NOA
(Aaeo?ii?, 1996; Iiaee I?eaai, 1997), ia 7io I?aeia?iaeiiio neiiic?oi?
ii i?aeoeiao ionea?eiiaeo ?aoeaioi??a (A?aeaiue, 1997), ia ni?eueiiio
can?aeaii? O?c?ieia?/ieo oiaa?enoa Aaeeeia?eoai?? ? *ao?? (I?aaa, 1998),
ia can?aeaii? Naeoi?a iieaeoey?ii? o?c?ieia?? ?inoeoooo o?c?ieia?? ?i.
I.I. Aiaiiieueoey IAI Oe?a?ie (1999).

Ioae?eaoe??

?acoeueoaoe ?iaioe iioae?eiaai? o 27 noaooyo a?o/eciyieo oa
i?aeia?iaeieo aeo?iae?a oa a 26 oacao iaoeiaeo neiiic?oi?a.

No?oeoo?a oa ianya aeena?oaoe??

Aeena?oaoe?y neeaaea?oueny c anooio, iaeyaeo e?oa?aoo?e, iieno iaoiae?a
aeine?aeaeaiiy, ?acoeueoao?a aeine?aeaeaiiy (8 ?icae?e?a), aiae?co ?
ocaaaeueiaiiy ?acoeueoao?a, aeniiae?a oa nieneo 284 aeei?enoaieo
e?oa?aoo?ieo aeaea?ae. ?iaioa aeeeaaeaia ia 278 noi??ieao, i?noeoue 2
oaaeeoe? oa ?ethno?iaaia 101 ?enoieii.

IAOIAeEEA AeINE?AeAEAIUe

Ia’?eoe aeine?aeaeaiue. Aeine?aee i?iaiaeeeeny ia iiiaeeiieeo
?cieueiaaieo oa eoeueoeaiaaieo ee?oeiao. Iiiaeeiie? AIE iiaeiaaeiueiai
oa?o ileum ii?nueei? naeiee ? uo?a iaea?aeoaaee ca aeiiiiiaith iaoiaeo
oa?iaioaoeaii? oa iaoai?/ii? ?cieyoe??. Iaaaee/e? oiaoi/ee i’yciai?
oeaieie iii?uaeeny o aaceaeueoe??aee ?ic/ei, ui i?noea eieaaaiaco (1
ia/ie), ni?aee ?ia?a?oi? o?eineio (1 ia/ie) ? ae/a/ee aeueaoi?i (1
ia/ie), ia 25-30 oaeeei i?e 36°N, i?ney /iai noa?aiii a?aeieaaeeny a?ae
oa?iaioo ? aaaaoi?aciai i?iioneaeeny /a?ac neeyio i?iaoeo. Aeey
aeae?eaiiy AIE ileum iiaiia?iaeaeaieo uo??a (a?e 1-3 aeiy, aaaa 5-9 a)
eiioeaio?aoe?y eieaaaiace aoea 0,7 ia/ie, aeanoace — 0,3 ia/ie, ae/a/iai
aeueaoi?io — 2 ia/ie, /an ?ieoaaoe?? neeaaeaa 13-17 oaeeei. Aeey
aei?ineeo uo??a (2,5-3 i?nyoey, aaaa 90-120 a) eiioeaio?aoe?? oa?iaio?a
ca?eueooaaeeny o aeaa ?ace, a /an ?ieoaaoe?? noaiiaea 50-60 oaeeei.

AIE oiieiai eeoa/ieeo ethaeeie (American Type Culture Collection 1692-
CRL) oo?eioaaeeny o iiaeeo?eiaaiiio eoeueoo?aeueiiio na?aaeiaeu?
Aetheueaaei (DMEM) ?c aeiaeaaaiiyi 10% ae/a/i? aia??iiaeueii? ne?iaaoee,
100 U/ie iai?oeee?io ? 100 U/ie no?aioii?oeeio. Aeei?enoiaoaaeeny
ee?oeie ianaae?a 16 ? 17.

Aeey iaea?aeaiiy ia?aeiii? eoeueoo?e iae?ii?a i?aei’yciaiai ieaoeaa
oiieiai eeoa/ieeo ii?nueei? naeiee aaiae?? cae?aeeny i?ney ia?iaee
oeaieie, ye iienaii aeua, ? oo?eioaaeeny a caieiaeai?e aoiinoa?? 5% NI2
i?e 37° N a na?aaeiaeu? 199 ?c aeiaeaaaiiyi 10% ?iaeoeaiaaii? oaieii
ae/a/i? aia??iiaeueii? ne?iaaoee, 33 iI aetheice, 100 U/ie iai?oeee?io,
0,1 ia/ie no?aioii?oeeio, 0,1% ooia?ciia ? 0,5% aaioai?oeeia.
Aeei?enoiaoaaeeny iae?iie, ye? ciaoiaeeeeny a eoeueoo?? a?ae 5 aei 15
aei?a.

?a?no?aoe?y ?iiieo no?oi?a. Aeey aeine?aeaeaiiy ?ioaa?aeueieo ?iiieo
no?oi?a canoiniaoaaany noaiaea?oiee iaoiae o?enaoe?? iioaioe?aeo ?
aioo??oiueiee?oeiii? ia?ooc?? ca aeiiiiiaith neeyii? i?e?ii?iaoee a
eiio?ao?aoe?? whole-cell (Hamill et al., 1981). Aeoeai?noue iiiaeeiieeo
?iiieo eaiae?a aeine?aeaeoaaeany o eiio?ao?aoe?yo cell-attached ?
outside-out. O aeayeeo aenia?eiaioao aeei?enoiaoaaeany iaoiaeeea
iiaea?eii? patch-?a?no?aoe?? (eiia?iaoe?y whole-cell ? cell-attached
eiio?ao?aoe?e). I?ney caiiaiaiiy a?aeiia?aeiei ?ic/eiii i?iaoee iaee
ii?? 1-3 IIi. Iine?aeiaiee ii?? neeaaeaa o na?aaeiueiio 8,4 IIi ?
eiiiainoaaany ia 80%. O a?eueo?e /anoei? aenia?eiaio?a aeei?enoiaoaaany
i?aeneethaa/ o?enaoe?? iioaioe?aeo Axopatch 200A ? ?ioa?oaen Digidata
1200, ea?iaaiee i?ia?aiith pClamp 6.0 (Axon Instruments). Aeai?
aiae?coaaeeny ca aeiiiiiaith i?ia?ai pClamp 6 ? MicroCal Origin 5.0.
Aeey ?a?no?aoe?? oaeaeeeo ?iiieo no?oi?a (iai?eeeaae, OOO-/ooeeaee Na+
no?oi) neaiae o?eueo?oaaany ca aeiiiiiaith o?eueo?a Aannaey 4ai ii?yaeeo
c /anoioith c??co 5 eAoe ? caienoaaany i?e 40 eAoe; i?e ?a?no?aoe??
aeoeaiino? iiiaeeiieeo ?iiieo eaiae?a oe? aaee/eie aoee 1-2 eAoe ? 5-10
eAoe, a?aeiia?aeii, a i?e ?a?no?aoe?? eao?iiieo no?oi?a — 1 ? 5 eAoe,
a?aeiia?aeii.

Oaoi?ea oioie?co. Na?oei enaiiiiai? eaiie (niaeao o?eaae?noth 1 in,
300<<380 ii) oieonoaaeiny ia ee?oeio, ui iiia?aaeiuei ia?oocoaaeany ia iaioa 5 oaeeei ?ic/eiii c “caged“ ?a/iaeiith. ?ioaineai?noue niaeaoo ?aaoethaaeany oeyoii ci?ie iai?oae ca?yaeo eiiaeainaoi?a (ICE), oiae? ye iiiaio iiaea/? niaeaoo caaeaaaany neio?i?iioeuenii ?c ?aaoeueiaaiith cao?eieith a?aeiinii ?iioeueno o?enaoe?? iioaioe?aeo. A?aenioie eiiaa?n?? neeaaeaa 2,2±0,3 i?e ICE 40A ? 8,6±0,4 (n=5) i?e ICE 75. Neeaae ? ci?ia ?ic/ei?a. Ii?iaeueiee ciai?oi?e ?ic/ei i?noea (iiieue/e): 120 NaCl, 6 KCl, 2,5 CaCl2, 1,2 MgCl2, 11,5 aetheica, 10 HEPES (pH 7,4; NaOH). Aeey ?a?no?aoe?? Na+ no?oi?a KCl cai?iyany ia CsCl, a CaCl2 - ia MgCl2. O ee?oeiao, aea aoee i?enooi? Na+ eaiaee (iae?iie, AIE ileum uo?a), Na2+ no?oie ?a?no?oaaeeny i?e cai?i? NaCl ? KCl ia 130 iI OAA-Cl, a a on?o ?ioeo aeiaaeeao - i?e cai?i? KCl ia CsCl. Eao?iii? no?oie i?e aeoeaaoe?? ionea?eiiaeo ?aoeaioi??a ?a?no?oaaeeny o ?ic/ei? oaeiai neeaaeo (iiieue/e): 120 CsCl, 12 aetheica, 10 HEPES (pH 7,4; CsOH). ?ic/ei o i?iaooe? iaa oaeee neeaae: 85 KCl, 30 KH2PO4, 1 MgSO4, 1 Na2ATO, 5 e?aaoei, 20 aetheica, 10 HEPES (pH 7,4; NaOH), 0,05-5 AAOA a caeaaeiino? a?ae iaoe aenia?eiaioo. Aeey ?a?no?aoe?? Na2+ no?oio KCl ? KH2PO4 cai?ithaaeeny ia 115 iI CsCl. Aeey ?a?no?aoe?? K+ ? Ca2+ aai Na+ no?oi?a o AIE ileum uo?a ?ic/ei i?noea a?aeiia?aeii 130 iI KCl aai CsCl, aeiaaaeyeiny oaeiae 0,1 iI oeAIO. ?ic/ei aeey aeine?aeaeaiiy eao?iiiiai no?oio i?e aeoeaaoe?? ionea?eiiaeo ?aoeaioi??a i?noea 80 CsCl, 1 MgCl2, 1 Na2AOO, 5 e?aaoei, 10 BAPTA, 4,6 CaCl2 ([Ca2+]i=100 nM), 20 aetheica, 10 HEPES (pH 7,4; CsOH). Ciai?oi?e ?ic/ei i?iyany o anueiio ia’?i? aenia?eiaioaeueii? eaia?e (~0,4 ie) ca /an, ui ia ia?aaeuoaaa 1 n. O aeayeeo aenia?eiaioao, iai?eeeaae, i?e aei??? eaoaioiiai ia??iaeo aeieeiaiiy eao?iiiiai no?oio i?e aie?eaoe?? ea?aaoie?io, aoea iio??aia a?eueoa oaeaee?noue aie?eaoe??. A oeeo aeiaaeeao aeei?enoiaoaaeany i’aciaeaeo?e/ia iiceoe?eia nenoaia PCS-250, yea aeicaieyea ci?ieoe ?ic/ei ia i?ioyc? i?eaeecii 1 in. Noaoenoe/i? iaoiaee. ?acoeueoaoe noaoenoe/iiai aiae?co aenia?eiaioaeueieo aeaieo i?aaenoaaeai? ye na?aaei? a?eoiaoe/ia ± noaiaea?oia iiieeea na?aaeiueiai a?eoiaoe/iiai (n - e?euee?noue aei???a). Aeey noaoenoe/iiai ii??aiyiiy aeei?enoiaoaaany t-e?eoa??e Nouethaeaioa, ?icoiaeaeaiiy i?eeiaeeny ye aeinoia??i? i?e P<0,05. Aeai? iienoaaeeny a?aeiia?aeieie iaoaiaoe/ieie ooieoe?yie c aeei?enoaiiyi i?ia?aiiiai caaacia/aiiy Origin. Eiioeaio?aoe?ei? caeaaeiino? oa aeoeaaoe?ei?/?iaeoeaaoe?ei? e?ea? iienoaaeeny, a?aeiia?aeii, oaeeie ??aiyiiyie: wmetafile801000900000397010000030017000000000005000000090200000000040000 0002010100050000000102ffffff00040000002e01180005000000310201000000050000 000b0200000000050000000c024004e00c1200000026060f001a00ffffffff0000100000 00c0ffffffaeffffffa00c0000ee0300000b00000026060f000c004d6174685479706500 00e00009000000fa02000010000000000000002200040000002d01000005000000140203 02c4020500000013020302950c17000000fb0280fe0000000000009001010000cc000200 1054696d6573204e657720526f6d616e2043797200ccdd040000002d0101000900000032 0a80023500010000005900da0009000000320a7201d305010000005900da000900000032 0a9103d405010000004100ea000a000000320a91033708020000004543ea000101170000 00fb0220ff0000000000009001010000cc0002001054696d6573204e657720526f6d616e 2043797200ccdd040000002d01020004000000f001010009000000320ae502c70b010000 005000880010000000fb0280fe0000000000009001000000020002001053796d626f6c00 02040000002d01010004000000f001020009000000320a80028301010000003d00d30009 000000320a9103a003010000002b00d30017000000fb0280fe0000000000009001000000 cc0002001054696d6573204e657720526f6d616e2043797200ccdd040000002d01020004 000000f00101000c000000320a7201f706030000006d6178002b01a800c3000a00000032 0a9103bf0402000000285b7e00820009000000320a9103c406010000005d008200090000 00320a91036d07010000002f006b0009000000320a9103360b0100000029007e00090000 00320a9103b802010000003100c00017000000fb0220ff0000000000009001000000cc00 02001054696d6573204e657720526f6d616e2043797200ccdd040000002d010100040000 00f00102000a000000320af1031a0a020000003530700070000a00000026060f000a00ff ffffff01000000000010000000fb021400090000000000bc02000000cc01020222537973 74656d00cc040000002d01020004000000f001010003000000000000ff00ffffff (1) wmetafile801000900000379010000030015000000000005000000090200000000040000 0002010100050000000102ffffff00040000002e01180005000000310201000000050000 000b0200000000050000000c024004e00f1200000026060f001a00ffffffff0000100000 00c0ffffffb6ffffffa00f0000f60300000b00000026060f000c004d6174685479706500 00f00009000000fa02000010000000000000002200040000002d01000005000000140200 02c3020500000013020002820f15000000fb0280fe000000000000900100000000040200 1054696d6573204e657720526f6d616e000067040000002d01010008000000320a8b03d2 0e010000007d0008000000320a8b03780d010000002f0008000000320a8b03c30c010000 0029000a000000320a8b03b804050000006578707b280008000000320a8b03b802010000 00310009000000320a6f016a08030000006d61780015000000fb0220ff00000000000090 01000000000402001054696d6573204e657720526f6d616e000067040000002d01020004 000000f001010008000000320aeb031b0c01000000320008000000320aeb03b70b010000 002f0008000000320aeb03350b01000000310015000000fb0280fe000000000000900101 0000000402001054696d6573204e657720526f6d616e000067040000002d010100040000 00f001020008000000320a8b031a0e010000006b0008000000320a8b035b0a0100000056 0008000000320a8b03000801000000560008000000320a6f012907010000005900080000 00320a60021f0001000000590010000000fb0280fe000000000000900100000002000200 1053796d626f6c0002040000002d01020004000000f001010008000000320a8b036a0901 0000002d0008000000320a8b03a003010000002b0008000000320a60028c01010000003d 000a00000026060f000a00ffffffff01000000000010000000fb021400090000000000bc 02000000cc0102022253797374656d00cc040000002d01010004000000f0010200030000 000000000000000000 (2) aea Y - aei??thaaia aaee/eia (no?oi aai iaia?aiia i?ia?aei?noue), Ymax - ?? iaeneiaeueia cia/aiiy, EC50 ? V1/2 - ia?aiao?e, i?e yeeo Y=Ymax, a p ? k - /eiieee iaoeeo e?eai?. ?acoeueoaoe AeINE?AeAEAIUe ?iii? no?oie iaia?aie iae?ii?a ?io?aio?aeueieo aaiae??a. Aeaeo?e/ia aeoeai?noue i?aioa?aeueieo iae?ii?a ? oith ii/aoeiaith eaieith, ui i?ecaiaeeoue aei aea?eueiaiiy o ia?aiaeo cae?i/aiiyo aoeaoeeoie?io ? caioneo oe?eiai eaneaaeo neeaaeieo ?aaeoe?e, iiina?aaeeiaaieo aeoeaaoe??th ionea?eiiaeo ?aoeaioi??a AIE ? eii?aeeioth/eo nei?i/oaaeueio aeoeai?noue eeoa/ieeo. Oa?aeoa? aeoeaiino? a?ae??ciy?oueny a ??ciiiai?oieo ae?eyieao o?aaiiai o?aeoo ? i?ae iae?iiaie ??cieo oei?a. Oe? aeai? aacothoueny a iniiaiiio ia aenia?eiaioao ?c aeei?enoaiiyi i?e?iaeaeo?iaeieo iaoiae?a ?a?no?aoe?? (Wood, 1989), oiae? ye ?c canoinoaaiiyi iaoiaeo patch-clamp aeine?aeaeoaaeeny eeoa iae?iie iiaiia?iaeaeaieo oaa?ei, aeanoeaino? yeeo iiaeooue ?noioii a?ae??ciyoeny a?ae iae?ii?a aei?ineeo oaa?ei. A oiiaao o?enaoe?? oieo a?eueo?noue aeine?aeaeoaaieo iae?ii?a aaia?oaaee eeoa 1-2 iioaioe?aeo ae?? c ianooiiith o?eaaeith ne?aeiaith a?ia?iiey?ecaoe??th, ui aeicaieyei a?aeianoe ?o aei AH/oei 2 iae?ii?a. Iioaioe?aeea?iaai? iao???a? ? eaeueoe??a? no?oie Ao?aei?e no?oi neeaaeaany c? oaeaeeiai ? iia?eueiiai eiiiiiaio?a. Oaeaeeee no?oi cieeaa o aaciao???aiio ?ic/ei? ? aeieoaaany oao?iaeioieneiii (OOO, IC50=10,7 iI), aea caa??aaany a aaceaeueoe??aiio ?ic/ei? ? aoa oaeei /eiii ?aeaioeo?eiaaiee ye Na+ no?oi. Iaai?ioe, iia?eueiee eiiiiiaio no?oio caa??aaany a aaciao???aiio ?ic/ei? ? ci?ithaaany ii aiie?ooae? a caeaaeiino? a?ae [Ca2+]o ? aoa ?aeaioeo?eiaaiee ye ICa. INa aeinyaaa iaeneiaeueiiai cia/aiiy i?e 10 iA (2,2±0,3 iA, n=15). I?e a?eueo iiceoeaieo iioaioe?aeao aianie ICa ca?eueooaaany, iaeneioi oieo niinoa??aaany i?e 10 iA (0,8±0,1 iA, n=15). I?e aeaiiey?ecaoe?? Na+ eaiaee ?iaeoeaoaaeeny c iaei??th iino?eiith /ano, yea ciaiooaaeany a?ae 161 in i?e 70 iA aei 2,3 in i?e 30 iA. Aeo?ae ?c ?iaeoeaaoe?? iienoaaany iino?eieie /ano 7,3±1,1 in i?e 100 iA; 21,8±5,1 in i?e 80 iA ? 43,7±11,1 in i?e -60 i (n=4); i?e 60 iA aeyaeyany oaeiae a?eueo iia?eueiee eiiiiiaio ?c iino?eii? /ano 288±30 in (n=4). Caeaaei?noue noaoe?iia?ii? ?iaeoeaaoe?? a?ae iioaioe?aeo iienoaaeany e?eaeie Aieueoeiaia (??aiyiiy 2) c oaeeie ia?aiao?aie: V1/2 -55,6 ? 38,9 iA; k 6,4 ? 14,4 iA aeey INa e ICa, a?aeiia?aeii. Aaee/eia V1/2 aeey noaoe?iia?ii? ?iaeoeaaoe?? Na+ eaiae?a aeecueea aei iioaioe?aeo niieith a aeaieo iae?iiao (o niiei? ia ?iaeoeaiaaii 70% eaiae?a), ui i?eionea? ooieoe?iiaeueio ?ieue Na+ eaiae?a o aaia?aoe?? iioaioe?ae?a ae?? ? a iiaeoeyoe?? caoaeaeaiiy i?ae /an ye oaeaeeeo, oae ? iia?eueieo neiiioe/ieo a?aeiia?aeae, ui iathoue o aeaieo iae?iiao aeoaea ae?aaeaiee oa?aeoa?. E?iaoeea ?iaeoeaaoe?? ? aeoiaeo c ?iaeoeaaoe?? aeinoaoiuei oaeaeea o ii??aiyii? c e?iaoeeith CINI ? AINI. O /anoei? iae?ii?a (a?ey 30%) a iaeano? iaaaoeaieo iioaioe?ae?a niinoa??aaany iaaaeeeee iecueeiii??aiaee ICa ?c oaeaeeith e?iaoeeith ?iaeoeaaoe?? (100 in), ui iaaaaeoaaa O-no?oi. Aenieiii??aiaee Ca2+ no?oi ia?aiineany, i/aaeaeii, /a?ac Ca2+ eaiaee N-oeio. Oeae no?oi eeoa /anoeiai i?eai?/oaaany i?oaaeei?iii (100 mI ia 35±4%, n=6), i?ioa iiai?noth aeieoaaany 2 mI w-CgTX. I?e cai?i? Ca2+ ia Ba2+ ao?aeiee no?oi cia/ii ca?eueooaaany aac oiia?eueiaiiy eiai ?iaeoeaaoe??. *ooeea?noue aei iai?aai?/ieo aeieaoi??a Ca2+ eaiae?a (Gd3+>Cd2+>Ni2+) oaeiae
a?aeiia?aeaea o/ano? N-oeio Ca2+ eaiae?a.

Aeaiee oei Ca2+ eaiae?a ? aaaeeeaith «i?oaiith» aeey ??ciiiai?oieo
iae?iia?aaeao/ee?a. 5-IO, iaae?aoi? iia?eueiiai caoaeaeoth/iai ?,
iiaeeeai, aaeuei?aiiai INI o AH/oei 2 iae?iiao i?eai?/oaaa ICa ia 40%
(100 I). Aaii?no A1 ?aoeaioi??a 2oei?aaeaiic?i i?eai?/oaaa ICa a?eueo
i?ae ia 50% (IN50=210 iI). Oanoe c aeiaeaaaiiyi aei ?ic/eio o i?iaooe?
AOOS ? AAeOS iieacaee, ui o ia?aaea/? neaiaeo aa?ooue o/anoue G-a?eee.

Eae??a? no?oie

Aoee aeyaeai? ? aeine?aeaeai? /ioe?e oeie K+ no?oi?a: iia?euei? no?oie
ao?aeiiai ? cao?eiaiiai aeo?aeiiai aei?yieaiiy ? oaeaee? oeio IA ?
Ca2+-caeaaeiee no?oi. A?aeiia?aei? K+ eaiaee a?ae??ciyeeny ii
iioaioe?aecaeaaeiino? ? oa?iaeieia?/ieo aeanoeainoyo, ui aeicaieyei
cae?enithaaoe ?icae?eaiiy no?oi?a.

K+ no?oi ao?aeiiai aei?yieaiiy aoa ?cieueiaaiee ?c aeei?enoaiiyi 200 mI
OOO ? aaceaeueoe??aiai ciai?oiueiai ?ic/eio c iaoith i?eai?/aiiy INa,
ICa ? IK(Ca). O oeeo oiiaao aeaiiey?ecoth/? ?iioeuene aeeeeeaee
iia?eueiee K+ no?oi cao?eiaiiai aei?yieaiiy (IK,dr), oiae? ye
a?ia?iiey?ecoth/? ?iioeuene aeoeaoaaee E+ no?oi ao?aeiiai aei?yieaiiy
(?en. 1). I?ia?aei?noue iaia?aie i?e 30 iI K+ (EE=34 iA) iienoaaeany
??aiyiiyi (2) ?c aaee/eiaie V1/2=105 iA ? k=8,8 iA. Aeoeaaoe?y IK,ir
i?enei?thaaeany o a-?ac i?e a?ia?iiey?ecaoe?? iaia?aie ia 31 iA.

OAA+ aeieoaaa IK,dr, aea ia IK,ir, oiae? ye Cs+ naeaeoeaii i?eai?/oaaa
IK,ir (IC50=58 mI).

?ai?oa iayai?noue oaeaeeiai IA o iaia?ai? iae?ii?a i?aei’yciaiai ieaoeaa
ia?aaeaa/aeiny ia i?aenoaa? ae?aaeaieo aoaeo?a 4-A? ia oi?io iioaioe?aeo
ae?? ? ne?aeiai? a?ia?iiey?ecaoe?? (Hirst et al., 1985). IA ?a?no?oaaany
i?e 30 iA, aea IK,dr a?aenooi?e. Aeoeaaoe?y ? ?iaeoeaaoe?y IA
iienoaaeeny ??aiyiiyi (2) ?c oaeeie ia?aiao?aie: V1/2 = 95,5 iA, k =
7,2 iA aeey ?iaeoeaaoe?? ? V1/2 = 45,9 iA, k=16,8 iA aeey aeoeaaoe??.
Iino?eia /ano aeoiaeo c ?iaeoeaaoe?? ciaiooaaeany a a-?ac i?e
a?ia?iiey?ecaoe?? iaia?aie ia 36 iA, a?ae 1,4±0,3 n i?e 90 iA aei
0,4±0,1 n i?e 140 iA (n=3). IA i?eai?/oaaany ia 40 ? 80% i?e aeiaeaaaii?
a?aeiia?aeii 3 ? 10 iI 4A?, oiae? ye 10 iI OAA+ ia aieeaaa ia oeae
no?oi.

Aeuaiienai? aenia?eiaioe i?iaiaeeeeny i?e 5 iI AAOA o i?iaoi/iiio
?ic/ei?. I?e ciaioaii? eiioeaio?aoe?? aei 0,3 iI aeieeaa oaeiae IK(Ca)
(?en. 2A). Caeaaei?noue eiai aiie?ooaee a?ae iaia?aiiiai iioaioe?aeo
aoea oaeith ae, ye ? aeey ICa. IK(Ca) i?a o?eaaoe aei 3,5 n — oea
ocaiaeaeo?oueny c oyaeaiiyie i?i eiai oeaio?aeueio ?ieue o aaia?aoe??
o?eaaei? ne?aeiai? a?ia?iiey?ecaoe??, ui ? oa?aeoa?iith iciaeith aeaiiai
oeio iae?ii?a. Aeine?aeaeaiiy aeanoeainoae IK,ir aeicaiey? i?eionoeoe
eiai aaaeeeao o/anoue, ii?yae ?c IK(Ca), o aaia?aoe?? o?eaaei?
a?ia?iiey?ecaoe??, ui a naith /a?ao a?eueo iiaii iiynith? oeae neeaaeiee
i?ioean.

Caaaeueia oa?aeoa?enoeea ?iiieo no?oi?a iaia?aie AIE oiieiai eeoa/ieeo

Oa?aeoa? aeaeo?e/ii? aeoeaiino? AIE ?noioii a?ae??ciy?oueny a
caeaaeiino? a?ae ?oiueiai oeio, a aeey iaeiioeiieo AIE iienai? cia/i?
aeaeia? a?aei?iiino? (Kuriyama et al., 1998). ?icoi?iiy iaoai?ci?a
oie?ia?a?/iiai eiio?ieth AIE eeoa/ieeo iiaei aacoaaoeny o?eueee ia
aeaoaeueiiio iiia?aaeiueiio aeine?aeaeaii? ?o caaaeueieo
aeaeo?io?c?ieia?/ieo aeanoeainoae. A oeeo aenia?eiaioao aoee ciaeaeai?
aaaeeea? aeaeia? oa a?eia? a?aei?ie a i?e?iae? ? aeanoeainoyo ?iiieo
no?oi?a.

Ileum ii?nueei? naeiee

O AIE, ?cieueiaaieo ?c iiaeiaaeiueiai ileum ii?nueei? naeiee, o
a?aenooi?noue aeoeaaoe?? ?aoeaioi??a ao?aeiee no?oi ia?aiineoueny /a?ac
iioaioe?aeea?iaai? Ca2+ eaiaee L-oeio ? iiai?noth aeieo?oueny
i?oaaeei?iii o eiioeaio?aoe?? 1 I, a iniiaiei eiiiiiaioii aeo?aeiiai
no?oio ? IK(Ca) (?en.2A). I?e iecuee?e eiioeaio?aoe?? AAOA a i?iaooe?
aeieeaee niiioaii? aeo?aei? no?oie (NAN), aia?oa iienai? aeey AIE
jejunum ? aooii? a?oa??? e?ieeea (Benham & Bolton, 1986). ?aaa?n?y NAN
niinoa??aaeany i?e EK, NAN aeieoaaeeny OAA+, i?e cai?i? E+ ?iiaie Cs,
i?e i?aeaeuaii? eiioeaio?aoe?? AAOA o i?iaoi/iiio ?ic/ei? aai i?e
aeaeaeaii? Ca2+ ?c ciai?oiueiai ?ic/eio, a oaeiae i?e ae?? aeieaoi?a
??aiiae?iiaeo ?aoeaioi??a ?ooai??aiai /a?aiiiai. Oaeei /eiii, ?iiia
i?e?iaea ? iaoai?ci aeieeiaiiy NAN o AIE ileum a?aeiia?aeathoue ?ioei
oeiai aeaaeaiueeeo i’yc?a, oiaoi NAN iaoiiaeai? neio?iiiith aeoeaaoe??th
Ca2+-caeaaeieo K+ eaiae?a o iaeiio o?aaiaio? iaia?aie i?e niiioaiiiio
eieae?ciaaiiio aea?eueiaii? Ca2+ ?c aioo??oiueiee?oeiieo aeaii (N?).

Ni?aa?aeiioaiiy i?ae ICa ? IK(Ca) iieacaia ia ?en. 2A. Aiii ia
iano?eueee iaeiicia/ia, ye, iai?eeeaae, o iae?iiao (?en. 2A), ?
i?eioneaei aeiaeaoeiaee iaoai?ci iineeaiiy ae?? Na2+ ca ?aooiie
Na2+-?iaeoeiaaiiai aea?eueiaiiy Na2+ (E?AE). Oea caneoaiaoaaei a?eueo
aeaoaeueiiai aiae?co, ?acoeueoaoe yeiai iienai? ieae/a o ii??aiyii? c
aeanoeainoyie Ca2+ no?oio.

Ileum uo?a

Ia a?aei?io a?ae AIE ileum ii?nueei? naeiee a ee?oeiao iiaeiaaeiueiai
i?ioa?eo ileum uo?a i?e?iaea ao?aeiiai no?oio aoea cia/ii neeaaei?oith.
A?i neeaaeaany c Na+ ? Ca2+ eiiiiiaio?a. Ca2+ eaiaee aoee i?aaenoaaeai?
aeaiia iiioeyoe?yie, iecueei- ? aenieiii??aiaeie. A?aeiiniee aianie oeeo
iiioeyoe?e caeaaeaa a?ae a?eo oaa?eie. Aiie?ooaea ia?oiai ia
ci?ithaaeany i?e cai?i? Ca2+ ia Aa2+, a ae?oaiai — ca?eueooaaeany ia
80±10% (n=8). Iaeaeaa eiiiiiaioe ICa ia ci?ithaaeeny i?e aeiaeaaaii? 1 I
i?oaaeei?io. Iai?aai?/i? aeieaoi?e Ca2+ eaiae?a Cd2+ ? Ni2+ ii-??ciiio
aieeaaee ia iecueei- ? aenieiii??aiaee INa. Oae, Cd2+ o eiioeaio?aoe??
10 I i?eai?/oaaa aenieiii??aiaee ICa ia 50% ? ia aieeaaa ia
iecueeiii??aiaee ICa. Iaai?ioe, Ni2+ o eiioeaio?aoe?? 500 I iaeaea
iiai?noth aeieoaaa iecueeiii??aiaee ? o?eueee ia 40% — aenieiii??aiaee
eiiiiiaio. ?noioi? a?aei?ie niinoa??aaeeny oaeiae aeey noaoe?iia?ii?
?iaeoeaaoe??. Aaee/eie V1/2 ? k aoee, a?aeiia?aeii, -60,6 ? 8,8 iA aeey
iecueei- ? -49,0 ? 13,6 iA aeey aenieiii??aiaiai ICa. A?ae??ciyeanue
oaeiae ? e?iaoeea a?aeiiaeaiiy c ?iaeoeaaoe??: i?e -80 iA
iecueeiii??aiaee ICa oe?eeii a?aeiiaethaaany ca 2-5 n, oiae? ye
aenieiii??aiaee — ca 20-30 n. O noi? oe? aeai? na?ae/eee i?i
aaoa?iaaii?noue Ca2+ eaiae?a o iaia?ai? AIE ileum uo?a. A?eueo oiai,
aoei aeyaeaii, ui a aei?ineeo oaa?ei caa??aa?oueny eeoa aenieiii??aiaee
ICa.

I?e aeaeaeaii? ?ii?a Ca2+ ?c ciai?oiueiai ?ic/eio niinoa??aaany oaeaeeee
ao?aeiee no?oi, ?aeaioeo?eiaaiee ye INa. Oeae no?oi aoaeoeaii aeieoaaany
OOO (IC50=4,5 iI). Noaoe?iia?ia ?iaeoeaaoe?y INa oa?aeoa?ecoaaeany
ia?aiao?aie: V1/2=-60 iA ? k=10 iA. A?aeiiaeaiiy c ?iaeoeaaoe?? aoei
oaeaeeei (iino?eia /ano 18-47 in o ae?aiacii? iioaioe?ae?a a?ae -90 aei
-60 iA). Ne?ae cacia/eoe, ui INa, ia a?aei?io a?ae ICa, cono??/a?oueny
eeoa a aeayeeo oeiao aeaaeaiueeeo i’yc?a (Kuriyama et al., 1998), a aeey
AIE eeoa/ieeo oeae no?oi iaie aoa aeyaeaiee aia?oa.

O AIE iiaiia?iaeaeaieo oaa?ei niinoa??aaany cao?eiaiee ? oaeaeeee
aeo?aei? no?oie. Inoaii?e aoa iiae?aiei aei IA o iae?iiao. OAA+
ia?aaaaeii aeieoaaa cao?eiaiee K+ no?oi, oiae? ye 4-A? naeaeoeaii
aeieoaaa oaeaeeee eiiiiiaio. Aoaeo 4-A? aoa neeaaeiei ? iineethaaany a
/an? i?e a?ia?iiey?ecaoe?? iaia?aie. Noaoe?iia?ia ?iaeoeaaoe?y IA
oa?aeoa?ecoaaeany V1/2=-70,8 iA ? k=7,7 iA. Iino?eia /ano a?aeiiaeaiiy c
?iaeoeaaoe?? ciaiooaaeany i?e a?ia?iiey?ecaoe?? iaia?aie ? neeaaeaea
90±5 in (n=13) i?e -80 iA. IA niinoa??aaany a 93% aeine?aeaeoaaieo AIE
(n=240). Ia a?aei?io a?ae AIE ileum ii?nueei? naeiee NAN niinoa??aaeeny
eeoa a iaei?e ee?oei?. I/aaeaeii, o AIE iiaiia?iaeaeaieo uo??a
Ca2+-caeaaei? K+ eaiaee i?aeoe/ii a?aenooi?. Iaai?ioe, o AIE aei?ineeo
uo??a NAN niinoa??aaeeny /ano?oa, a aeanoeaino? IA ia ci?ithaaeeny.

AIE oiieiai eeoa/ieeo ethaeeie

A AIE oiieiai eeoa/ieeo ethaeeie (91 ee?oeia, ianaae? 16-17) ICa ?
IK(Ca) aoee a?aenooi?, ui i/aaeaeii iia’ycaii c aeayeith iiaeeo?eaoe??th
aeanoeainoae ee?oei o eoeueoo?? (Owens, 1995). O na?aea?cieueiaaieo
ee?oeiao i?enooi? Ca2+ eaiaee L-oeio (Xiong et al., 1995), aea
Ca2+-caeaaei? K+ oaae a?aenooi? (Farrugia et al., 1993). ?iii? no?oie a
oe?e eoeueoo?? ee?oei aoee i?aeoe/ii ia aea/aieie. Cai?ia Na+ ia Cs+
i?ecaiaeeea aei iiaiiai i?eai?/aiiy ao?aeiiai no?oio, iacaaaeath/e ia
i?enooi?noue o ciai?oiueiio ?ic/ei? 10 iI Ca2+ aai Ba2+. E??i oiai,
ao?aeiee no?oi aeieoaaany OOO c IC50=56 iI. Ii nai?i aeanoeainoyi INa
aoa iiae?aiei aei INa a AIE ileum uo?a.

Iaei??? c oe?eaaeo iniaeeainoae oeeo ee?oei aoa ?icaeoie ao?aeieo
eao?iiieo no?oi?a i?e aeaeaeaii? aeaiaaeaioieo eao?ii?a ?c ciai?oiueiai
?ic/eio. Ia?oee eiiiiiaio aeoeaoaaany i?e a?ia?- (IHA), a ae?oaee — i?e
aeaiiey?ecaoe?? iaia?aie (IDA). Ine?eueee oe? no?oie ?icaeaaeeny cia/ii
iia?euei?oa, i?ae oea aoei iio??aii aeey ci?ie ciai?oiueiai ?ic/eio,
iiaeia aoei i?eionoeoe ye iiaeeeaee iaoai?ci ?oiuei? aeoeaaoe?? ianeaia
aeniaaeaiiy aioo??oiueiee?oeiieo Ca2+ caianiee?a (CRAC-iiae?ai? eaiaee).
Ia ei?enoue oeueiai na?ae/eea ? aeieoth/a ae?y SK&F 96365. Oaeee
iaoai?ci aoiaeo Ca2+ ? iniiaiei o ee?oeiao ??cieo oei?a, iniaeeai a
iacaoaeeeaeo ee?oeiao i?e a?aenooiino? ?ioeo oei?a Ca2+ eaiae?a (Parekh
& Penner, 1997). Aeey AIE oeae iaoai?ci ?ai?oa aoa cai?iiiiiaaiee ia
i?aenoaa? aei???a [Ca2+]i i?e ae?? aaii?no?a ?aoeaioi??a ? oaineaa?a?ia,
aea ni?iae aei??o a?aeiia?aeiiai ?iiiiai no?oio aeyaeeeny aaconi?oieie.
IDA aoa a?eueo /ooeeaei aei [Ca2+]i o ii??aiyii? c IHA. Aaee/eie IC50
neeaaeaee 20 I aeey IHA ? 311 iI aeey IDA. A?ae??ciyeanue ? ?iiia
naeaeoeai?noue: K+ > Cs+ > Na+ aeey IHA ? Na+ > K+ >> Cs+ aeey IDA.

Oaeei /eiii, o AIE oiieiai eeoa/ieeo ?niothoue ?noioi? a?aei?ie a
aeni?an?? oeo aai ?ioeo ?iiieo eaiae?a a caeaaeiino? a?ae aeaeo ? a?eo
oaa?eie, a oaeiae i?e ci?i? ee?oeiiiai oaiioeio a i?ioean?
eoeueoeaoaaiiy ee?oei. Ao?aei? no?oie iiaeooue ia?aiineoeny /a?ac
OOO-/ooeea? Na+ eaiaee ? Ca2+ eaiaee ??cieo oei?a, a oaeiae /a?ac
ianaeaeoeai? eao?iii? eaiaee, ui aeoeaothoueny i?e nionoioaii? N?.
Aeo?aei? K+ no?oie i?aaenoaaeai? iioaioe?aeea?iaaieie cao?eiaiei ?
oaeaeeei (oeia IA) no?oiaie, a oaeiae iioaioe?ae- ? Ca2+- caeaaeiei
IK(Ca).

Iaoai?cie aea?eueiaiiy Ca2+ ?c aioo??oiueiee?oeiieo aeaii AIE

I?e oie?ia?a?/i?e aeoeaaoe?? AIE ia?aeaeueii ?c aeaiiey?ecaoe??th
iaia?aie oa aoiaeii Ca2+ cciai? a?aeaoaa?oueny oaeiae aea?eueiaiiy Ca2+
?c N?, ui aeeth/a? ye E?AE, oae ? InsP3-?iaeoeiaaia aea?eueiaiiy Ca2+
(??AE) (Karaki et al., 1997). O aeine?aeaeoaaieo AIE ileum ii?nueei?
naeiee Ca2+ aeaii ? ni?eueiei aeey iaio i?ioean?a (Komori et al., 1995).
Iineeaiiy aoiaeo Ca2+ ca aeiiiiiaith E?AE ? o?c?ieia?/ia cia/ei?noue
oeueiai iaoai?cio a ??ciiiai?oieo AIE ca?ac ia aeeeeea? noii?ao, a
?icaeoie iaoiae?a ?a?no?aoe?? [Ca2+]i ca aeiiiiiaith eiioieaeueii?
oeoi?anoeaioii? i?e?ineii?? iieacaa aenieo i?inoi?iao ? oei/aniao
no?oeoo?iaai?noue Ca2+ neaiaeo. I?ioa aei iiiaioo ii/aoeo aeaieo
aeine?aeaeaiue aeey aeaaeaiueeeo i’yc?a o?c?ieia?/ia ?ieue E?AE eeoa
ia?aaeaa/aeany, a iniiaiiio ia i?aenoaa? ?a?no?aoe?? nei?i/oaaeueieo
?aaeoe?e i?e ae?? aaii?no?a ? eioa?io (Karaki et al., 1988).
Aenia?eiaioe ia ne?iiaaieo naiii?iii AIE na?ae/eee i?i oa, ui E?AE iiaea
aeoeaoaaoeny i?e [Ca2+]i>1 M, ui oaeei /eiii aeeeth/aei eiai
o?c?ieia?/io cia/ei?noue (Iino, 1989).

sse iiaeeeao no?aoaa?th aeine?aeaeaiiy aoei aeei?enoaii c?noaaeaiiy ICa
? IK(Ca), aai ICa ? eao?iiiiai no?oio, ui aeieea? i?e aeoeaaoe??
ionea?eiiaeo ?aoeaioi??a (IEAO). IEAO ei?aeth? ?c ci?iaie [Ca2+]i
iaa?oue a?eueo o?nii o ii??aiyii? c IK(Ca) (Komori et al., 1993), ?,
oaeei /eiii, iaeaeaa no?oie iiaee aooe ?ioa?i?aoiaai? ye ye?niee
iieaciee ??aiy [Ca2+]i.

?aaaia?aoeaiee oa?aeoa? E?AE

I?e o?eaae?e aeaiiey?ecaoe?? iaia?aie ?icaeaaany cao?eiaiee aeo?aeiee
no?oi (?en. 2A). Aiaeia?/iee no?oi aeieeaa ? i?e aie?eaoe?? eioa?io aai
oioie?c? «caged» InsP3 ona?aaeei? ee?oeie, ui iineoaeeei i?aenoaaith
aeey i?eiouaiiy i?i o/anoue ?ii?a Ca2+, ui aea?eueiththoueny c N?, a
aeoeaaoe?? oeueiai no?oio, ?aeaioeo?eiaaiiai ye IK(Ca). C?noaaeaiiy
e?iaoeee ICa ? IK(Ca), a oaeiae a?aeiia?aeieo aieueoaiia?ieo
caeaaeiinoae (?en. 2A) na?ae/eei i?i iai?yio ?ieue aoiaeo Ca2+ a
aeoeaaoe?? cao?eiaiiai IK(Ca). Eioa?i oe?iei aeei?enoiao?oueny ye
oa?iaeieia?/iee ?ino?oiaio aeey iiae?aiiai ?iaeo aeine?aeaeaiue, i?ioa
e??i aeoeaaoe?? ??aiiae?iiaeo ?aoeaioi??a o iaia?ai? N? a?i iiaea
aeeeeeaoe e ?io? aoaeoe. Ae?enii, aoei ciaeaeaii, ui o eiioeaio?aoe?? 10
iI eioa?i aeeeeeaa i?eai?/aiiy ICa i?eaeecii ia 30%. Oaeee aoaeo ia i?a
iiynieoe iiaia aeieoaaiiy cao?eiaiiai IK(Ca) o i?enooiino? eioa?io, yea
a??ia?aeii aeieeaei aiane?aeie nionoioaiiy N?. ?ineeiiee aeeaei?ae
??aiiaeei (5 I), ?ooai??aee /a?aiiee (10 mI) ? i?aeaeuaiiy
aioo??oiueiee?oeiii? eiioeaio?aoe?? Mg2+ aei 6 iI i?aeoe/ii oe?eeii
aeieoaaee cao?eiaiee IK(Ca). Aoei i/aaeaeiei, ui oeae no?oi aeieea?
aiane?aeie E?AE, ui aeoeao?oueny aoiaeii Ca2+ i?e aeaiiey?ecaoe??
iaia?aie.

Iiaeaeueo? aenia?eiaioe aoee ni?yiiaai? ia c’yniaoaaiiy aeanoeainoae
E?AE, aiae?coth/e i?e oeueiio cao?eiaiee IK(Ca) ? eiai ni?aa?aeiioaiiy c
aiie?ooaeith ICa. Aeo?aeiee no?oi, /ooeeaee aei ?ooai??aiai /a?aiiiai,
ii/eiaa ciaiooaaoeny i?e iioaioe?aeao, cia/ii a?eueo iiceoeaieo, i?ae
iiaeia aoei a i/?eoaaoe aeey “a?aaeoaeueiiai“ E?AE, i?iii?oe?eiiai
aoiaeia? Ca2+ (?en. 2A). O ?ioeo na??yo aenia?eiaio?a aoea aeine?aeaeaia
caeaaei?noue aiie?ooaee IK(Ca) a?ae /anoeiai ?iaeoeaiaaiiai aai /anoeiai
aeieiaaiiai i?oaaeei?iii ICa (?en. 3). Aeyaeeiny, ui cao?eiaiee IK(Ca)
ii/eia? ciaiooaaoeny ii aiie?ooae? eeoa i?ney i?eai?/aiiy ICa ia 80-95%.
Oe? ?acoeueoaoe, io?eiai? c aeei?enoaiiyi ??cieo aenia?eiaioaeueieo
i?aeoiae?a, aeacoaaee ia ?aaaia?aoeaiee oa?aeoa? i?ioeano E?AE o AIE
ileum ii?nueei? naeiee. Ao?ae Ca2+, iaa?oue iaaaeeeee, iiaea
a?ae?a?aaaoe ?ieue ioneiaiai iaoai?cio, ui aeoeao? E?AE. Naia iayai?noue
aeo?aeiiai no?oio, ui aeoeao?oueny i?e aeieeiaii? E?AE, na?ae/eea i?i
?noioia i?aeaeuaiiy [Ca2+]i ia aeiaeaoie aei aeeeeeaiiai aaciina?aaeiuei
ao?aeiei Ca2+ no?oiii, ? oaeei /eiii o?c?ieia?/io cia/ei?noue E?AE.

Ca2+-caeaaeia iiaeoeyoe?y ??AE

O AIE oi?ioaaiiy InsP3 i?e ae?? ??ciiiai?oieo aaii?no?a iia’ycaii c?
nei?i/aiiyi, ui iaoiiaeaii i?aeaeuaiiyi [Ca2+]i o iane?aeie ??AE. ?iie
Na2+ oaeiae iiaeooue ca’ycoaaoeny c InsP3 ?aoeaioi?aie ? iiaeoethaaoe
?oith aeoeai?noue, o oaeee niin?a ?aaoethth/e ??AE ca i?eioeeiii
cai?ioiiai ca’yceo (Bezprozvanny & Ehrlich, 1995). O noaoe?iia?ieo
oiiaao caeaaei?noue aeoeaiino? InsP3 ?aoeaioi??a a?ae eiioeaio?aoe??
Na2+ ? -ia?aciith c iaeneioiii a?ey 300 iI. Aaaeeeai a?aecia/eoe, ui
e?iaoeea ae?? Ca2+ ia ??AE oaeiae ? neeaaeiith ? o oe?eiio aea/aia
iaaaaaoi a??oa. O a?eueoino? ?ia?o aeine?aeaeaiiy i?iaiaeeeeny c
aeei?enoaiiyi iaee?oeiieo aenia?eiaioaeueieo iiaeaeae (aaceeoee N?,
ne?iiaai? ee?oeie, InsP3 ?aoeaioi?e o a?neiyo) aai ae ia iacaoaeeeaeo
ee?oeiao (iai?eeeaae, iioeeoe Xenopus). Oae? i?aeoiaee iathoue nai?
ia?aaaae, i?ioa aiie ia aeicaieythoue a?aeiia?noe ia caieoaiiy i?i
iiaeeeao iiaeoeyoe?th ??AE ?iiaie Na2+, ui aoiaeyoue o ee?oeio /a?ac
iioaioe?aecaeaaei? Na2+ eaiaee.

C iaoith c’ynoaaiiy oeeo ieoaiue InsP3 ?aioiai aea?eueithaaany c
?ia?oiiai «caged» InsP3 i?e niaeaoo na?oea ? iaeii/anii ?a?no?oaaany
IK(Ca), ii aiie?ooae? yeiai ioe?ithaaee ci?ie eiioeaio?aoe?? ?ii?a Na2+
c aioo??oiuei? iiaa?oi? iaia?aie. A caeaaeiino? a?ae ?ioaineaiino?
na?oea niinoa??aaeeny iiii- aai aeaioaci? a?aeiia?ae?. Iaei??? c
iiaeeeaeo i?e/ei aaia?aoe?? aeaioacieo a?aeiia?aeae iiaea aooe
aeoeaoth/a ae?y Na2+, ui aea?eueiy?oueny ia ?aii?e noaae?? ??AE, ia
ianooiiee i?ioean eiai aea?eueiaiiy. Ae?enii, aeaiiey?ecoth/ee
?iioeuene, ui noi?iaiaeaeoaaeeny aoiaeii Na2+, i?aeneethaaee ae?th
InsP3. Oeae aoaeo ii/eiaany ia i?ioyc? 30-100 in i?ney caaa?oaiiy
aeaiiey??caoe??, aeinyaaa iaeneioio i?eaeecii ca 250 in, a iio?i
ci?iyany i?eai?/aiiyi a?aeiia?ae? ia InsP3. O aeine?aeao c aeaiia
niaeaoaie yeui /an i?ae ieie noaiiaea 0.5-1 n, ae?oaa a?aeiia?aeue aoea
cia/ii a?eueoith; i?e /an? 3-6 n niinoa??aaeiny ?? iiaia i?eai?/aiiy.
Iiaia a?aeiiaeaiiy o na?aaeiueiio a?aeaoaaeiny ca 60 n, aea o eiaei?e
ie?ai?e ee?oei? a?aeiiaeaiiy aoei ii oeio ona aai i?/iai ? iiaei aooe
a?eueo oaeaeeei (10-20 n). Aiaeia?/ii oeueiio, i?ney aea?eueiaiiy InsP3
NAO i?eai?/oaaeeny, a iio?i iinooiiai a?aeiiaeyeeny, ui na?ae/eei i?i
caiiaiaiiy aioo??oiueiee?oeiieo Ca2+ aeaii ? iiaeeea?noue niiioaiiiai
aea?eueiaiiy Ca2+ ca o/anoth ??aiiaeeiiaeo ?aoeaioi??a. I?ioa
a?aeiia?ae? ia InsP3 aoee a?aenooi? iaaaaaoi a?eueo o?eaaeee /an, a ?oi?
a?aeiiaeaiiy ciiao oaee a?aeaoaaeiny ?aioiai ?, ye i?aaeei, ca
i?eioeeiii “ona aai i?/iai” (?en. 4A). ?acoeueoaoe oeeo aenia?eiaio?a
aeacothoue ia aaaeeeao ?ieue iioaioe?aecaeaaeiiai aoiaeo Na2+ /a?ac Na2+
eaiaee L-oeio o iiaeoeyoe?? InsP3-?iaeoeiaaiiai aea?eueiaiiy Na2+ ?,
oaeei /eiii, o aeieeiaii? inoeeeyoe?e [Ca2+]i i?e oie?ia?a?/iiio
caoaeaeaii? a?noea?aeueieo aeaaeaiueeeo iyc?a. Ia ei?enoue oeueiai
na?ae/eee ? aenia?eiaioe, a yeeo InsP3 aea?eueiyany o ??ci? oace
inoeeeyoe?e IEAO, ui aaciina?aaeiuei iia’ycai? c inoeeeyoe?yie [Ca2+]i.
Oae, ia iaeneioi? inoeeeyoe?? a?aeiia?aeue aoea a?aenooiy (F1 ? F3 ia
?en. 4A), oiae? ye o i?ii?aeeo i?ae inoeeeyoe?yie a?aeiia?aeue cae/aeii
aoea oaei? ae aiie?ooaee, ye ? niiioaii? inoeeeyoe?? (F2 ? F4 ia ?en.
4A).

Iaoai?cie oie?ia?a?/ii? aeaiiey?ecaoe?? AIE

Caaaeueia oa?aeoa?enoeea eao?iiiiai no?oio i?e aeoeaaoe?? ionea?eiiaeo
oie?ii?aoeaioi??a

Ca o?c?ieia?/ieo oiia oie?ia?a?/ia aeaiiey?ecaoe?y noi?iaiaeaeo?oueny ye
aoiaeii Ca2+ cciai?, oae ? eiai aea?eueiaiiyi ?c N?. Aeieeath/?
inoeeeyoe?? [Ca2+]i aeeeeeathoue inoeeeyoe?? IEAO (?en. 4A). Aeaoaeueiee
a?io?ce/iee ? oa?iaeieia?/iee aiae?c aeanoeainoae IEAO aoa iiaeeeaee
o?eueee i?e noaoe?iia?ieo oiiaao. Oaeei /eiii, o iiaeaeueoeo
aenia?eiaioao eiioeaio?aoe?y Ca2+ o ee?oei? o?enoaaeany ia ??ai? 100 iI,
ui i?eaeecii a?aeiia?aea? ??aith o noai? niieith, ?c aeei?enoaiiyi 10 iI
AA?OA/4,6 iI CaCl2 o i?iaoi/iiio ?ic/ei?. Ne?ae cacia/eoe, ui i?e
aeei?enoaii? 10 iI AA?OA aac aeiaeaaaiiy Ca2+, oiaoi a oiiaao
iai?e?iaeii iecueei? eiioeaio?aoe?? Ca2+ o oeeoiieaci? ee?oeie, ye
aaia?aoe?y IEAO, oae ? i?eai?/aiiy ICa oe?eeii aeieoaaeeny. Oaeei /eiii,
iaeaeaa iaoai?cie iio?aaothoue aeayeiai i?i?iaeueiiai ??aiy Ca2+ o
ee?oei?.

Ine?eueee aeine?aeaeoaai? eaiaee ia naeaeoeai? aeey iaeiiaaeaioieo
eao?ii?a, aenia?eiaioe i?iaiaeeeeny c aeei?enoaiiyi neiao?e/ieo Cs+
?ic/ei?a (ECs=0 iA) c iaoith aeieoaaiiy K+ no?oi?a. E??i oiai, o
a?eueoino? aenia?eiaio?a aeaiaaeaioi? eao?iie aeaeaeyeeny c ciai?oiueiai
?ic/eio, uia aeeeth/eoe ?o aieea.

Ea?aaoie?i (EO) ca?eueooaaa aiie?ooaeo IEAO a?aeiia?aeii aei ??aiyiiy
(1) c na?aaei?ie ia?aiao?aie: AC50=7,8 mI, iaeneiaeueia i?ia?aei?noue
Gmax=23,3 iN, p=1,4 (n=114). A?noia?aie ?iciiae?e?a oeeo ia?aiao??a
aeia?a iienoaaeeny e?eaeie Aaona, ui na?ae/eei i?i a?aenooi?noue ??cieo
iiioeyoe?e ee?oei.

Cia/iee ?ioa?an yaeyee niaith iioaioe?aecaeaaei? ?aeaenaoe?? IEAO i?e
?aioiaeo ci?uaiiyo iaia?aiiiai iioaioe?aeo, i?e?iaea yeeo caeeoaeany
iaeiaea/aiith (?en. 5). ?aeaenaoe?? no?oio iienoaaeeny iaeiith
aeniiiaioith c iino?eieie /ano aeey ??cieo ee?oei a?ae aeae?eueeio
aeanyoe?a aei aeae?eueeio nio i?e?naeoiae. O nenoai? ?aoeaioi? — G a?eie
— ?iiiee eaiae iiaeooue aeieeaoe cia/ii neeaaei?o? aca?iiae?? o
ii??aiyii? c a?eueo i?inoith neooaoe??th, eiee ?iiiee eaiae ? i?noea
ca’ycoaaiiy aaii?noa i?aaenoaaeai? iaei??? iae?iiieaeoeith. Ia?oa eaiea
a eaioethc? iiae?e, ui aaaea aei a?aee?eaaiiy eaiaeo, oiaoi aca?iiae?y
aaii?noa ? ?aoeaioi?a, o i?eioeei? iiaei a iiynieoe ?aeaenaoe?? IEAO ca
oiiae iioaioe?aecaeaaeiino? ca’ycoaaiiy aaii?noa. I?ioa oaea i?eiouaiiy
aoei iaeieiia??iei, ine?eueee oaeaeeino? aeoeaaoe?? ? aeaaeoeaaoe??
no?oio i?e aie?eaoe?? ? a?aeieaaii? EO aoee a 10-100 ?ac?a iia?euei?o? o
ii??aiyii? c eiai iioaioe?aecaeaaeieie ?aeaenaoe?yie (?en. 5).

Iioaioe?aecaeaaei?noue IEAO iiaea a?aeia?aaeaoe aeanoeaino? naiiai
eaiaeo, aea iaa?oue ia?o? oanoe iieacaee, ui aca?iiae?y aaii?noa c
?aoeaioi?ii a?ae?a?a? eeth/iao ?ieue. Oae, e?iaoeea ?aeaenaoe?e no?oio
ci?ithaaeany a caeaaeiino? a?ae eiioeaio?aoe?? EO ? a?ae /ano i?ney eiai
aeiaeaaaiiy aai aeaeaeaiiy. E??i oiai, a?aeaoaaeeny ?noioi? ci?ie o
oi?i? noaoe?iia?ii? aieueoaiia?ii? oa?aeoa?enoeee (?en. 6). I?e 3 mI
no?oi i?e 120 iA i?aeoe/ii iiai?noth aeaaeoeaoaaany, oiae? ye i?e 300 mI
aieueoaiia?ia caeaaei?noue ?c Uiiae?aii? ia?aoai?thaaeany o a?eueo
e?i?eio, a i?ioean aeaaeoeaaoe?? no?oio i?e 120 iA aeoaea
niia?eueithaaany. Aiae?c o oa?i?iao e?eaeo aeoeaaoe?? eao?iiii?
i?ia?aeiino? iieacaa, ui i?e i?aeaeuaii? eiioeaio?aoe?? aaii?noa e?eaa
ci?uoaaeany a iaeanoue a?eueo iaaaoeaieo iioaioe?ae?a, a a i?ioean?
aeanaineoecaoe?? i?e aeniei? eiioeaio?aoe?? EO aiia iinooiiai
iiaa?oaeany aei naiai aeo?aeiiai iieiaeaiiy ia a?n? iioaioe?ae?a (?en.
6A). Aaee/eia V1/2 o na?aaeiueiio ci?uaeany ia 36 iA (aa??aoe?? a?ae 17
aei 89 iA) a?ae 70±5 iA aei 106±5 iA i?e i?aeaeuaii? eiioeaio?aoe?? EO
a?ae 3 aei 300 I (n=16). I?e oeueiio iaoee e?eai? ia i?iyany (k=19,3±0,9
iA). A?aeiia?aei? ci?ie niinoa??aaeeny ? o e?iaoeoe? ?aeaenaoe?? no?oio
i?ae /an nea/eo iioaioe?aeo aei 120 iA: aaee/eia ca?eueooaaeany a?ae
94±12 in (3 mI EO) aei 178±14 in (300 mI EO), a iio?i iinooiiai
ciaiooaaeany a i?ioean? aeanaineoecaoe?? aei 112±13 in (n=20).

?ieue G-a?ee?a a aeoeaaoe?? eao?iiieo eaiae?a ? a iiaeoeyoe?? ?o
aeanoeainoae

Iiaeia aoei i?eionoeoe, ui aieea eiioeaio?aoe?? EO ia oaeaee?noue ?
nooi?iue ?aeaenaoe?? ? ia iieiaeaiiy aeoeaaoe?eii? e?eai?
iiina?aaeeiaaiee aeoeaaoe??th G-a?ee?a. Eiioeaio?aoe?y aeoeaieo G-a?ee?a
aecia/a?oueny i?e an?o ?ioeo ??aieo oiiaao iayai?noth ? eiioeaio?aoe??th
o ee?oei? AOO, a ?o aeoeaaoe?y aoaeoeaii aeieo?oueny iaa?ae?ie?co?iei
aiaeiaii AAeO — AAeOS. Iaea?eueoa i?yiei oanoii aeaii? a?iioace aoei a
aeiaeaoeiaa aeoeaoaaiiy aai aeieoaaiiy G-a?ee?a i?e iino?ei?e
eiioeaio?aoe?? EO. I?e aeiaeaaaii? 1 iI “caged” AOO aei i?iaoi/iiai
?ic/eio 3 niaeaoe na?oea c iaaaee/eei ?ioa?aaeii aea?eueiyee i?eaeecii
0,4 iI AOO. Oea noi?iaiaeaeoaaeiny cia/iei ca?eueoaiiyi IEAO.
Niinoa??aaeeny ci?ie oi?ie aieueoaiia?ii? caeaaeiino?, oa?aeoa?i? aeey
i?aeaeuaiiy eiioeaio?aoe?? EO. Aea?eueiaiiy AAeOS aeeeeeaei i?ioeeaaei?
aoaeoe.

A?aeiii, ui i?e ae?? AOOS G-a?eee aeoeaothoueny iia?eueii ? i?aeoe/ii ia
cai?ioii, ui aeaaaei iiaeeea?noue a?eueo aeaoaeueii aeine?aeeoe ?ieue
aeoeaiaaieo G-a?ee?a o iiaeoeyoe?? aeanoeainoae eao?iiii? i?ia?aeiino?.
I?e aeiaeaaaii? AOOS aei i?iaoi/iiai ?ic/eio (0,2 iI) oaca aeoeaaoe??
IEAO cae/aeii o?eaaea 3-5 oaeeei i?ney i?i?eao iaia?aie i?ae i?iaoeith,
i?ney /iai no?oi eeoaany aeoaea noaa?eueiei ia i?ioyc? aeanyoe?a oaeeei.
I?e oeueiio niinoa??aaeany iioaioe?aecaeaaei?noue e?iaoeee aeoeaaoe??,
ui aoea aeoaea iiae?aiith aei aeoeaaoe?? IEAO ea?aaoie?iii: no?oi
ia?inoaa oaeaeoa onueiai i?e 80 iA, iia?euei?oa i?e 40 iA ? ua a?eueo
iia?eueii i?e 120 iA. Niinoa??aaany oe?eaaee oaiiiai ia?aoeio aiie?ooae
IEAO i?e -40 ? 120 iA. Oaeee aea ia?aoei niinoa??aaany ? o aeuaiienaieo
aenia?eiaioao i?e ae?? EO — ?aii?e ia ii/aoeo ae?? aaii?noo ? i?ci?e o
i?ioean? aeanaineoecaoe?? ?aoeaioi??a.

E?iaoeea ?icaeoeo no?oio a?aeiia?aeaea i?eiouaiith i?i ??ci? aeiiae
noiniaii aeoeaiaaieo G-a?ee?a i?e ??cieo iioaioe?aeao. A?aeiia?aeii aei
oe??? a?iioace, i?e 80 iA IEAO iaee?aua a?aeia?aaea? aeania i?ioean
ca?eueoaiiy ?oiuei? eiioeaio?aoe??, oiae? ye i?e 40 ? 120 iA
niinoa??aa?oueny i?ioean eiiia?aoeaii? aca?iiae?? aeae?eueeio
aeoeaiaaieo iieaeoe G-a?eea c eaiaeii. sse a?aeiii, eiiia?aoeai?noue
aca?iiae?e o nenoai? i?eionea? neaiiaeaeio e?iaoeeo, naia oea ?
niinoa??aaeiny a aeaieo aenia?eiaioao i?e a?ae’?iieo iioaioe?aeao. Ii
nai?i aiie?ooaeiei, e?iaoe/iei ? iioaioe?aecaeaaeiei aeanoeainoyi
iaeaeaa no?oie i?e ?oi?e iaeneiaeuei?e aeoeaaoe?? (iaeneiaeueia
a?aeiia?aeue ia EO aai 3-5 oaeeei i?ney ii/aoeo ae?? AOOS) i?aeoe/ii ia
a?ae??ciyeeny.

Aieueoaiia?i? caeaaeiino? aeey IEAO i?e ae?? AOOS, io?eiai? c ?ioa?aaeii
20 n, iieacai? ia ?en. 7A. I/aaeaeii, ui ye ? o aeiaaeeo i?aeaeuaiiy
eiioeaio?aoe?? EO oi?ia e?eaeo ci?ith?oueny, a e?i?eia ae?eyiea
oa?aeoa?enoeee i?ia?aneaii iiaeiaaeo?oueny a iaeanoue a?ae’?iieo
iioaioe?ae?a. A?aeiia?aei? aeoeaaoe?ei? e?ea? iieacai? ia ?en. 7A —
niinoa??aaeiny iinooiiaa ca?eueoaiiy iaeneiaeueii? i?ia?aeiino? ?
ia?aeaeueiee cnoa o iaaaoeaio iaeanoue. ?aeaenaoe?? no?oio i?e 120 iA
oaae caciaaaee ci?i, oa?aeoa?ieo aeey iienaieo aeua i?e i?aeaeuaii?
eiioeaio?aoe?? EO, ye? iiaee iiynithaaoeny ci?iith V1/2 (?en. 7A).

?acoeueoaoe aeaieo aenia?eiaio?a iieacothoue, ui i?e aeoeaaoe?? G-a?ee?a
eao?iii? eaiaee ia o?eueee a?aee?eaathoueny, aea ? a?aeaoaa?oueny
iiaeoeyoe?y ?o aeanoeainoae. ?aeeiee i?ioean, ui caeaaeeoue a?ae
eiioeaio?aoe?? aeoeaiaaieo G-a?ee?a, aecia/a? e?euee?noue aeoeaiaaieo
eaiae?a (Gmax), iieiaeaiiy aeoeaaoe?eii? e?eai? ia a?n? iioaioe?ae?a ?
a?aeiia?aeii e?iaoeeo ?aeaenaoe?? i?e aeaiiio iioaioe?ae? (?en. 7A).

Aeey ??cieo oei?a eaiae?a (iai?eeeaae, NMDA ?aoeaioi?e o iae?iiao)
iieacaii, ui iae?i?ei? aieueoaiia?i? oa?aeoa?enoeee iiaeooue aeieeaoe
aiane?aeie iioaioe?aecaeaaeii? aeieoth/i? ae?? aeaiaaeaioieo eao?ii?a
aai i?ioii?a. A eiio?ieueieo aeine?aeao aoei ciaeaeaii, ui ciai?oi? ?iie
Ca2+, Mg2+ ? I+ aeineoue neeueii i?eai?/othoue IEAO, aea aeaoaeueiee
aiae?c iieacaa, ui aeai? aoaeoe iaoiiaeai? eeoa ci?iith aaee/eie
iiaa?oiaaiai iioaioe?aeo a ?acoeueoao? oeo?oaaiiy iaaaoeaii ca?yaeaeaieo
a?oi iiaeeco eaiaeo. Aeaye? a?aei?ie o ae?? Ca2+ ? Mg2+ (iai?eeeaae,
ci?ia e?ooecie aeoeaaoe?eii? e?eai? i?e aeiaeaaaii? Ca2+) iiaeia aoei
iiynieoe i?iieei?noth eaiaeo aei Ca2+ ? aeoeaoth/ith ae??th aei oiai, ye
Ca2+ anoeaa? ca’ycaoeny c BAPTA ona?aaeei? ee?oeie.

Aeanoeaino? iiiaeeiieeo eao?iiieo eaiae?a

Iaea?eueo i?yi? aeieace iioaioe?aecaeaaeiino? eao?iiieo eaiae?a iiaeia
aoei a iaea?aeaoe ia ??ai? ?a?no?aoe?? aeoeaiino? iiiaeeiieeo eaiae?a.
Ia ?en. 8A iieacai? i?eeeaaee oaeeo ?a?no?aoe?? i?e ??cieo iioaioe?aeao.
E??i iniiaiiai eaiaeo c i?ia?aei?noth a?ey 40-50 iN o aeayeeo aeiaaeeao
aoa i?enooi?e eaiae iaioi? i?ia?aeiino?, 89 iN, i?ioa eiai aeoeai?noue
ia aiae?coaaeany, oiio ui eiai aianie aoa iacia/iei.

?iciiae?e /an?a cae?eoiai ? a?aee?eoiai noai?a iaa aea? iino?eieo /ane,
ui na?ae/eoue i?i iayai?noue ye i?i?ioi aeaio cae?eoeo ? aeaio
a?aee?eoeo noai?a. Ne?ae cacia/eoe, ui niaae iae?ino?oio i?e cnoa?
iaia?aiiiai iioaioe?aeo aeia?a iienoaaany iaei??? aeniiiaioith (?en. 5,
7A) ?c iino?eiith /ano cae/aeii a iaaeao 20-200 in, ui a?aeiia?aea?
aeiaaio?eaaeiio a?aee?eoiio noaio. Ieoiia aaaa ei?ioeio?eaaeiai
a?aee?eoiai noaio, i/aaeaeii, iaaaeeea, a eiai /an aeeooy 1-2 in eeoa a
2-3 ?ace ia?aaeuo? iino?eio /ano ?ii?niiai a?oaoaeoo i?e ?a?no?aoe??
a?ae oe?ei? ee?oeie.

I?ia?aei?noue eaiaeo i?e iioaioe?aeao a?ae 70 aei 20 iA aoea o
na?aaeiueiio 42,1±3,7 iN (n=14) ? ia a?ae??ciyeany aeey oiia aeoeaaoe??
eaiaeo EO (38,5±6,9 iN, n=6) aai AOOS (44,8±4,1 iN, n=8) (P>0,4).
Caeaaei?noue a??ia?aeiino? a?aee?eoiai noaio (?i) a?ae iaia?aiiiai
iioaioe?aeo iienoaaeany ??aiyiiyi Aieueoeiaia (?en. 8A) c V1/2 aeey
??cieo ee?oei o iaaeao a?ae 45 aei 140 iA ? k a?ae 18 aei 24 iA. Oea
aeia?a ni?aa?aeiineeiny ?c a?aeiia?aeieie ia?aiao?ai aeoeaaoe?eieo
e?eaeo iae?ino?oio.

Aaeeeee ?ioa?an yaeyei c’yniaoaaiiy i?e/eie cieaeaiiy ?i i?e
a?ia?iiey?ecaoe?? iaia?aie. Aeey iae?ino?oio oea a?aeiia?aeaei
?aeaenaoe?? i?e 120 iA aei ??aiy, iaioa i?ae aiie?ooaea no?oio i?e 40 iA
(?en. 5), ? ae?aaeaeiny a U-iiae?ai?e oi?i? aieueoaiia?ii?
oa?aeoa?enoeee (?en. 6A). Ia ?en.8 ?i i?e 10 iA aoea 0,9 i?e
a?aenooiino? iiaea?eieo a?aee?eaaiue ia i?ioyc? aeineoue o?eaaeiai /ano
niinoa?aaeaiiy, oiaoi o o?aaiaio? iaia?aie ciaoiaeeany eeoa iaeei eaiae.
Oaeei /eiii, iiaeia aoei aiae?coaaoe eiai e?iaoeeo. Caeaaei?noue
iino?eieo /ano, ui iienothoue ?iciiae?ee /an?a aeeooy eaiaeo o
a?aee?eoiio ? cae?eoiio noaiao, iieacaia ia ?en. 8 A ? A, a?aeiia?aeii.
Iaeaeaa iino?ei? /ane aeey a?aee?eoiai noaio ciaiooaaeeny i?e
a?ia?iiey?ecaoe??, aea ia iano?eueee ?noioii (i?eaeecii a 2 ?ace) o
ii??aiyii? c? ca?eueoaiiyi iia?eueii? iino?eii? /ano aeey cae?eoiai
noaio (o 34 ?ace). Oaeaeea iino?eia /ano aeey cae?eoiai noaio i?aeoe/ii
ia caeaaeaea a?ae ??aiy iaia?aiiiai iioaioe?aeo, ui i?eionea? iino?ei?
/ania? ?ioa?aaee ona?aaeei? ia/ee. Oaeei /eiii, iniiaiee aoaeo cieaeaiiy
iaia?aiiiai iioaioe?aeo iieyaa? a ca?eueoaii? /ano aeeooy eaiaeo a
o?eaaeiio cae?eoiio noai?, ui a?aeiia?aea? ca?eueoaiith ?ioa?aaeo i?ae
ia/eaie. I?e oeueiio /an aeeooy o a?aee?eoiio noai? ciaioo?oueny — aeey
iae?ino?oio oea i?ecaiaeeoue aei i?enei?aiiy e?iaoeee ?aeaenaoe?? i?e
ca?eueoaii? aiie?ooaee a?ia?iiey?ecoth/eo ?iioeuen?a.

Oaeei /eiii, aeanoeaino? iiiaeeiieeo eaiae?a oe?eeii iiyniththoue
iioaioe?aecaeaaei? ?aeaenaoe?? ? neeaaeio oi?io aieueoaiia?ii?
oa?aeoa?enoeee ?ioaa?aeueiiai IEAO.

Iaoai?cie aeanaineoecaoe?? eao?iiii? i?ia?aeiino?

Aeanaineoecaoe?y a?aeiia?aeae, ui aeieeathoue i?e aeoeaaoe?? iaia?aiieo
?aoeaioi??a, ? aaaeeeaei o?c?ieia?/iei caoeniei ? aaeaioeaiei ee?oeiiei
iaoai?ciii ? yaey? niaith neeaaeiee ? oe?eaaee a?io?ce/iee oaiiiai, oiio
ui iieaeoey?i? iaoai?cie ? iaaecae/aeii ??ciiiai?oieie ? ia oe?eeii
c’yniaaieie (Grady et al., 1997). O aenia?eiaioao ii aeanaineoecaoe??
IEAO aoa aeyaeaiee i?eioeeiiai iiaee iaoai?ci, iaoiiaeaii? ae/a?iaiiyi
caiano AOO o ee?oei? i?e ?? ?ioaineaiiio a?ae?ie?c? o i?ioean?
aeoeaaoe?? G-a?ee?a. O aeine?aeaeaiiyo ia ?ioeo oeiao ee?oei oaeee
iaoai?ci ia i?iyaeyany (Mubagwa et al., 1994), ui iiynithaaeiny aenieith
nii??aeiai?noth G-a?ee?a aei AOO. Cia/ia ca?eueoaiiy IEAO i?e
aea?eueiaii? AOO ?c “caged” AOO o iiia?aaei?o aenia?eiaioao na?ae/eei
i?i iayai?noue cia/iiai “?aca?ao” eao?iiieo eaiae?a ? iaaeoeaieo
G-a?ee?a aiane?aeie iaiaaeaii? e?eueeino? iieaeoe AOO.

Ianaiia?aae aoee i?iaiae?ciaai? caeaaeiino? aiie?ooaee IEAO a?ae
eiioeaio?aoe?? EO aac aeiaeaaaiiy ? c aeiaeaaaiiyi 1 iI AOO aei
i?iaoi/iiai ?ic/eio. E?ea? eiioeaio?aoe?y-aoaeo i?e iiaoi?ieo
aie?eaoe?yo EO oa?aeoa?ecoaaeeny ciaioaiiyi iaeneiaeueii? i?ia?aeiino?,
ui aoei noaoenoe/ii aeinoia??iei o?eueee i?e a?aenooiino? AOO.
Niinoa??aaeany eeoa oaiaeaioe?y aei c?inoaiiy AN50. Oaeei /eiii,
iayai?noue AOO iaea a iniiaiiio cia/aiiy aeey aaee/eie Gmax, yea
a?aeiia?aea? iaeneiaeueii iiaeeeaiio aeey aeaii? ee?oeie e?eueeino?
aeoeaieo eaiae?a. Ooieoe?y aeania ionea?eiiaiai ?aoeaioi?a i?e
aeanaineoecaoe?? i?aeoe/ii ia ci?ithaaeany. Aaaeeeai a?aei?oeoe, ui i?e
iayaiino? AOO o aioo??oiueiee?oeiiiio ?ic/ei? aeuaiienai? ci?ie oi?ie
aieueoaiia?ii? caeaaeiino? ? aaee/eie V1/2 o i?ioean? aeanaineoecaoe??
(?en. 6) aoee iiai?noth a?aenooi?. Oaea noaa?euei?noue niinoa??aaeany ?
aeey AOOS-?iaeoeiaaiiai no?oio, ui ia aeeaii, ine?eueee o oeueiio
aeiaaeeo AOO aeey aeoeaaoe?? G-a?ee?a ia iio??aai.

C iaoith a?eueo aeaoaeueiiai c’ynoaaiiy ?ie? G-a?ee?a o i?ioean?
aeanaineoecaoe?? IEAO aei i?iaoi/iiai ?ic/eio aeiaeaaaeeny ??ciiiai?oi?
aoai?iia? ioeeaioeaee. Ne?ae cacia/eoe, ui aiie?ooaea, e?iaoeea ? oi?ia
aieueoaiia?ii? caeaaeiino? IEAO ia iaeneioi? a?aeiia?ae? caeeoaeeny
i?aeoe/ii aac ci?i, a iniiai? aoaeoe ioeeaioeae?a aeyaeyeeny o?eueee o
/an? ii i??? aeanaineoecaoe?? IEAO (?en. 9). Aeanaineoecaoe?y cia/ii
i?enei?thaaeany i?e aeiaeaaaii? 50 I AAeOS ? niia?eueithaaeany i?e
aeiaeaaaii? 1 iI AOO. Iaea?eueoa iia?eueiei aoa niaae no?oio,
aeoeaiaaiiai AOOS. O oeeo aeiaaeeao a?aeaoaaeany ci?ia eeoa ?ici??o Gmax
aac ?noioieo ci?i iieiaeaiiy aeoeaaoe?eii? e?eai? ia a?n? iioaioe?ae?a.

Aaaeeeai oaeiae a?aei?oeoe, ui oaeaee?noue aeanaineoecaoe?? caeaaeaea
a?ae iaia?aiiiai iioaioe?aeo. Aeanaineoecaoe?y aoea i?aeoe/ii a?aenooiy
i?e 80 iA (ca aeiyoeii, eiee aeiaeaaaany AAeOS), aea cia/ii
i?enei?thaaeany i?e a?ia?iiey?ecaoe?? iaia?aie (?en. 9). Oea aeiaeaoeiai
i?aeoaa?aeaeoaaei aeuacaaaeaio a?iioaco i?i oa, ui iaa?oue iaaaeeea
eiioeaio?aoe?y aeoeaiaaieo G-a?ee?a aeinoaoiy aeey a?aee?eaaiiy
eao?iiieo eaiae?a i?e iiceoeaieo iioaioe?aeao.

Cia/iee ?ioa?an iaei aeine?aeaeaiiy i?ioeano aeanaineoecaoe?? ia ??ai?
ci?ie aeoeaiino? iiiaeeiieeo eaiae?a. Oe? aenia?eiaioe i?iaiaeeeeny a
eiio?ao?aoe?? “outside-out” ?c aeiaeaaaiiyi 1 iI AOO aei i?iaoi/iiai
?ic/eio a iino?ei?e i?enooiino? 50 mI EO o ciai?oiueiio ?ic/ei?. Aeey
iae?ino?oi?a ca oaeeo oiia oa?aeoa?iei aoei ciaioaiiy iaeneiaeueii?
i?ia?aeiino?, ui cae/aeii ?ioa?i?aoo?oueny ye ciaioaiiy e?eueeino?
aeoeaieo eaiae?a, aac ci?ie ?ioeo ia?aiao??a aeoeaaoe?eii? e?eai? (V1/2
aai k). Ine?eueee, ye iieacaii aeua, aeoeaaoe?eia e?eaa aecia/a?oueny
caeaaei?noth ?i a?ae iaia?aiiiai iioaioe?aeo (?en. 8A), iiaeia aoei
i/?eoaaoe iino?ei?noue ?i i?e o?eniaaiiio iioaioe?ae?. Aenia?eiaioaeuei?
?acoeueoaoe i?aeoaa?aeaeoaaee oe? i?eiouaiiy. sseui ia ii/aoeo
aenia?eiaioo o aeine?aeaeoaaiiio o?aaiaio? iaia?aie aeyaeyeiny ye
i?i?ioi 4 aeoeaieo eaiaee, oi c /anii caeeoaany eeoa iaeei aeoeaiee
eaiae, aea ?i i?e oeueiio ia ciaiooaaeany. I?ia?aei?noue eaiaeo oaeiae
ia ci?ithaaeany.

?ieue i?aeoei?a ionea?eiiaeo ?aoeaioi??a o ?icaeoeo IEAO

Aeine?aeaeaiiy iaoai?ci?a aeanaineoecaoe?? IEAO aeicaieeei noai?eoe
iaae?eio aenia?eiaioaeueio nenoaio aeey i?iaaaeaiiy e?euee?nieo
oa?iaeieia?/ieo aeine?aeaeaiue ia iiiaeeiieeo AIE. A on?o aenia?eiaioao
aeaiiai ?icae?eo aei i?iaoi/iiai ?ic/eio aeiaeaaaeiny 1 iI AOO. Aiae?c
aacoaaany ia aei??ao aaee/eie AN50 aeey EO aei ? i?ney aie?eaoe??
aioaaii?noa ionea?eiiaeo ?aoeaioi??a. Caaea/a aecia/aiiy oeio
ionea?eiiaiai ?aoeaioi?a, ui aeoeao? eao?iiiee eaiae, oaeoe/ii
caiaeeeany aei c’ynoaaiiy ?ie? I2 ? I3 ?aoeaioi??a, oiio ui, ye aaea
a?aecia/aeiny, o AIE ileum i?enooi? eeoa oe? aeaa i?aeoeie ?aoeaioi??a.

Aeey aiae?co aoee aeei?enoai? I2-naeaeoeai? aioaaii?noe iaoieo?ai?i,
a?iaaoeei ? o??i?o?ai?i ? I3-naeaeoeai? aioaaii?noe p-F-HHSiD, 4-DAMP ?
cai?oaiaoeei. Iio?aaa aeei?enoaiiy aeae?eueeio aioaaii?no?a iaoiiaeaia
a?aenooi?noth aaniethoii? naeaeoeaiino?. E?euee?niee aiae?c i?iaiaeeany
c aeei?enoaiiyi ??aiyiiy Oeeaea, iaaaaeaiiai ia ?en. 10, aea DR — oea
a?aeiioaiiy AN50 i?e ae?? aioaaii?noa ? o eiio?ie?, [B] — eiioeaio?aoe?y
? Kb — eiinoaioa aeenioe?aoe?? aioaaii?noa. Ia ?en. 10 iieacaii, ye
i?eeeaae, aenia?eiaio ii aecia/aiith aaee/eie Kb aeey iaoieo?ai?io ?
eiai aiae?c o ?aieao oai??? Oeeaea. On? ?io? I2-naeaeoeai? aioaaii?noe
ae?yee aiaeia?/iei /eiii, oiaoi niinoa??aaany ia?aeaeueiee cnoa
eiioeaio?aoe?eii? e?eai? aac nooo?aiai ciaioaiiy iaeneiaeueii?
a?aeiia?ae?. Oea na?ae/eei i?i eiieo?aioiee oei aeieoaaiiy, a
ni?anoaaeaiiy io?eiaieo aaee/ei eiinoaio aeenioe?aoe?? ?c a?aeiieie aeey
ca’ycoaaiiy c I2 ? I3 ?aoeaioi?aie (?en. 11) aaccaia?a/ii na?ae/eei i?i
i?eioeeiiao ?ieue I2 ?aoeaioi??a o a?aee?eaaii? eao?iiieo eaiae?a.

Iaaiaee, on? I3-naeaeoeai? aioaaii?noe o iecueeeo eiioeaio?aoe?yo cia/ii
ciaiooaaee iaeneiaeueio a?aeiia?aeue, i?aeoe/ii ia ci?ithth/e aaee/eio
AN50 aeey EO, a i?e a?eueo aenieeo eiioeaio?aoe?yo aeeeeeaee aeayea
ca?eueoaiiy AN50, ui iiaeia aoei iiynieoe ianaeaeoeaiith ae??th ia I2
?aoeaioi?e. Oe?eaai, ui ao?ii?i, eeane/iee ianaeaeoeaiee eiieo?aioiee
aeieaoi?, aeeeeeaa iaeaeaa oeie aoaeo?a. sse ? aioaaii?noe I2
?aoeaioi??a, ao?ii?i i?eaiaeea aei ia?aeaeueiiai cnoao eiioeaio?aoe?eii?
e?eai? a?aeiia?aeii aei Kb1 iI ? iaeii/anii, ye ? aioaaii?noe I3
?aoeaioi??a, neeueii i?eai?/oaaa iaeneiaeueio a?aeiia?aeue.

Oaeei /eiii, eao?iii? eaiaee a?aee?eaathoueny o ?acoeueoao? aca?iiae??
aaii?noa c ?aoeaioi?aie M2 oeio (ioneiaee iaoai?ci), i?ioa iaeii/ania
aeoeaaoe?y I3 ?aoeaioi??a neeueii aieeaa? ia oeae i?ioean ? aecia/a?
iaeneiaeueio e?euee?noue ooieoe?iiaeueieo eaiae?a (aeica?eueiee
iaoai?ci).

Iiaeaeue eao?iiiiai no?oio

Iioaioe?aecaeaaei?noue /ooeeaino? aei aaii?noo ? e?iaoeee eao?iiiiai
no?oio

Iioaioe?aecaeaaei?noue caeaoiino? aeoeaiaaieo G-a?ee?a i?aeo?eioaaoe
eao?iiiee eaiae o a?aee?eoiio noai? iiaea a?aeia?aaeaoeny o ??ci?e
/ooeeaino? aei aaii?noo, a oaeiae o ??ci?e e?iaoeoe? no?oio a
caeaaeiino? a?ae aaee/eie iaia?aiiiai iioaioe?aeo. Ae?enii, oanoe
iieacaee, ui i?e ci?i? iioaioe?aeo a?ae -50 aei 50 iA niinoa??aaany
cia/iee cnoa eiioeaio?aoe?eii? caeaaeiino? aiie?ooaee IEAO oa?e iaioeo
eiioeaio?aoe?e EO. Aaee/eia AN50 ciaiooaaeany i?eaeecii o 20 ?ac?a, a?ae
11 I i?e 50 iA aei 0,55 I i?e 50 iA. Oeae aoaeo aoa oe?eeii cai?ioiei ?
eaaei a?aeoai?thaaany ia iaei?e ? o?e aea ee?oei?.

Ciaioaiiy oyaii? eiinoaioe aeenioe?aoe?? i?e aeaiiey?ecaoe??, o aeaiiio
aeiaaeeo a??ia?aei?oa onueiai aeey ?aaeoe?? ooai?aiiy eiiieaeno
aeoeaiaaiee G-a?eie/eao?iiiee eaiae, oai?aoe/ii iiaeiii
noi?iaiaeaeoaaoeny i?enei?aiiyi aeoeaaoe?? e oiia?eueiaiiyi
aeaaeoeaaoe?? no?oio. Ia iaei?e ? o?e aea ee?oei? EO (50 I) iiaeaaaany
i?e iioaioe?aeao -50 ? 50 iA ca aeiiiiiaith iaaeoaeaeei?
i’aciaeaeo?e/ii? nenoaie. I?e aeaiiey?ecaoe?? e?iaoeea aeoeaaoe?? IEAO
i?enei?thaaeany i?eaeecii o 4 ?ace, a e?iaoeea aeaaeoeaaoe?? IEAO i?e
a?aeieaaii? EO oiia?eueithaaeany i?eaeecii o 5 ?ac?a. Oe?eaai
a?aecia/eoe, ui noia?iee aoaeo i?enei?aiiy aeoeaaoe?? e oiia?eueiaiiy
aeaaeoeaaoe?? aeaaaa /eiiee 20, ui aeecueei a?aeiia?aea? 16-20 e?aoiiio
ciaioaiith AN50 i?e oeo aea iioaioe?aeao. Eaoaioiee ia??iae a?aeiia?ae?
oaeiae caeaaeaa a?ae iaia?aiiiai iioaioe?aeo ? c?inoaa i?eaeecii a?ae
160 in i?e 50 iA aei 360 in i?e -50 iA.

?ai?oa ?iiaa ? ?caiaa?a (1990) aeey oi?iaeueiiai iieno
iioaioe?aecaeaaeiino? eao?iiii? i?ia?aeiino? canoinoaaee i?i?iaeueio
noaio ?aaeoe??, cai?iiiiiaaio Eano?ei ? Eaooeai (1957), a?aeiia?aeii aei
yei? iioaioe?aecaeaaei? ia?aoiaee a?aeaoaathoueny eeoa i?ae aeaiia
noaiaie eaiaeo, cae?eoei ? a?aee?eoei (?en. 12, ce?aa). Iaaaaeai? aeua
?acoeueoaoe aeine?aeaeaiiy aeoeaiino? iiiaeeiieeo eaiae?a na?ae/aoue, ui
oaea noaia ? aeoaea neeueiei ni?iuaiiyi ?aaeueii? neooaoe??, oiio ui ?
i?eiaeii? aeaa cae?eoeo ? aeaa a?aee?eoeo noaie eaiaeo. I?ioa, aeey
e?iaoeee ?aeaenaoe?e iae?ino?oio ae??oaeueia cia/aiiy iathoue ia?aoiaee
i?ae aeaiia aeiaaio?eaaeeie noaiaie, cae?eoei (?ioa?aae i?ae ia/eaie) ?
a?aee?eoei. Aeey ?ic?aooie?a (eiinoaioa oaeaeeino? cae?eaaiiy eaiaeo) ?
‘ (aoaeoeaia eiinoaioa oaeaeeino? a?aee?eaaiiy eaiaeo) aoee aeei?enoai?
aeai? aenia?eiaioo, iieacaiiai ia ?en. 7. Oaeee aiae?c iieacaa, ui i?e
aeoeaaoe?? G-a?ee?a aieiaiei /eiii a?aeaoaa?oueny ciaioaiiy , ui
a?aeiia?aea? ca?eueoaiith /ano aeeooy eaiaeo o a?aee?eoiio noai? (o
aeai?e noai? oeae /an a?aeiia?aea? 1/). I?e an?o ni?iuaiiyo, oeae
i?aeo?ae aeicaiey? iiynieoe oiia?eueiaiiy ?aeaenaoe?e eao?iiiiai no?oio
i?e iaeii/aniiio ia?aeaeueiiio cnoa? aeoeaaoe?eii? e?eai? a iaeanoue
iaio iaaaoeaieo iioaioe?ae?a ye ?aeeiee i?ioean.

Aiaeia?/ii i?yi?e aeoeaaoe?? G-a?ee?a i?e ae?? AOOS, ca?eueoaiiy
eiioeaio?aoe?? EO i?ecaiaeeei aei ciaioaiiy V1/2 ? oiia?eueiaiith
aeaaeoeaaoe?? IEAO i?ae /an a?ia?iiey?ecoth/eo ?iioeuen?a, a
aeanaineoecaoe?y aeeeeeaea i?ioeeaaei? aoaeoe (?en. 6). ? a oeeo
aeiaaeeao, o ?aieao aeuacaaaeaii? i?i?iaeueii? noaie ?aaeoe??,
a?aeaoaa?oueny a iniiaiiio ci?ia eiinoaioe oaeaeeino? cae?eaaiiy eaiaeo
(?en. 12, ieaeiy iaiaeue).

Iaoaiaoe/ia iiaeaethaaiiy iioaioe?aecaeaaeiino? eaoaioiiai ia??iaeo ?
e?iaoeee aeoeaaoe??, aeanaineoecaoe?? ? aeaaeoeaaoe?? eao?iiiiai no?oio

Ine?eueee iaia?aiia i?ia?aei?noue, a ioaea e aiie?ooaea oieo,
a?aeiia?aeii aei ??aiyiiy Aieueoeiaia (2) ? iae?i?eiith ooieoe??th V1/2,
iiaeia i/?eoaaoe, ui ye noaoe?iia?i? aieueoaiia?i? oa?aeoa?enoeee, oae ?
e?iaoeea no?oio i?e cnoa? V1/2 iiaeii? ?noioii ci?ithaaoeny.
Aenia?eiaioaeueii iiaeia aoei iii??yoe noaoe?iia?io aiie?ooaeo IEAO i?e
aeaio ??cieo iioaioe?aeao, V1 ? V2, c aenieith ?icae?euei?noth o /an?
oeyoii iiaea/? na??? ?iioeuen?a c ?ioa?aaeii a 1 n. Aeae? oeyoii
ianeeaaeieo aeaaa?a?/ieo ia?aoai?thaaiue iiaeia iieacaoe, ui aaee/eie
V1/2 ? Gmax aecia/athoueny oaeei /eiii:

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00 (3)

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(4 )

aea k — oaeoi? iaoeeo aeoeaaoe?eii? e?eai?. Ia ?en. 13A iieacaii
?acoeueoao iiae?aieo ?ic?aooie?a ia iniia? aei??thaaiiy aiie?ooaee IEAO
i?e -40 ? -120 iA i?ae /an aie?eaoe?? 50 I EO.

Aaaeeeaith ia?aaaaith iaoaiaoe/iiai iieno no?oio ? iiaeeea?noue eiai
a?aeoai?aiiy i?e ??cieo iioaioe?aeao (?en. 13A) ?c ianooiiei aiae?cii
io?eiaieo e?eaeo. Oaeee aiae?c iieacaa caeaaei?noue T1/2 aeoeaaoe?? IEAO
(/an aeinyaiaiiy 0,5Imax) (?en. 13A) ? oaeaeeino? aeanaineoecaoe??
no?oio (?en. 13A) a?ae iaia?aiiiai iioaioe?aeo. O iiaeae? oaeiae iayai?
ye oaiiiai “ia?aoeiaiiy” no?oi?a i?e ??cieo iioaioe?aeao, oae ?
caeaaei?noue eaoaioiiai ia??iaeo a?ae iioaioe?aeo (?en. 13A). Oaeei
/eiii, aeia?a a?aeoai?ththoueny an? e?iaoe/i? aeanoeaino? IEAO, ye?
niinoa??aaeeny o aeuaiienaieo aenia?eiaioao. Aeaia iiaeaeue aaia?aoe??
IEAO na?ae/eoue i?i oa, ui ?icaeyioo? e?iaoe/i? iniaeeaino? IEAO ii
nai?e i?e?iae? ? aoi?eiieie ? oe?eeii iiyniththoueny iniiaiei ia?aeiiei
i?ioeanii — cnoaii e?eai? aeoeaaoe?? ii a?n? iioaioe?ae?a.

Oie?ia?a?/iee eiio?ieue iioaioe?aeea?iaaiiai aoiaeo Ca2+

E??i a?aee?eaaiiy eao?iiieo eaiae?a aeoeaaoe?y ionea?eiiaeo ?aoeaioi??a
aeeeeea? oaeiae iiaeoeyoe?th iioaioe?aeea?iaaieo Ca2+ eaiae?a L-oeio.
?ai?oa iia?aeiieyeiny, ui i?eai?/aiiy ICa o AIE ileum ii?nueei? naeiee
ia /ooeeaa aei eieethoiiai oieneio (Unno et al. 1995). Ca o?c?ieia?/ieo
oiia i?eai?/aiiy ICa, ii?yae c aeoeaaoe??th a?ia?iiey?ecoth/iai IK(Ca)
i?e aea?eueiaii? Ca2+ ? aeanaineoecaoe?? IEAO iiaea neoaeeoe ua iaeiei
aaaeeeaei aaeaioeaiei ? caoeniei iaoai?ciii aeey iaiaaeaiiy aoiaeo Ca2+
o ee?oeio i?e oie?ia?a?/i?e aeaiiey?ecaoe??.

Iaoith aeaieo aeine?aeaeaiue aoei c’ynoaaiiy o/ano? G-a?ee?a ?
ii??aiyiiy aoaeo?a EO o a?aenooi?noue AOO ? i?e eiai aeiaeaaaii? aei
i?iaoi/iiai ?ic/eio o i?ioean? aeanaineoecaoe?? i?e iiaoi?ieo
aie?eaoe?yo EO.

Aeey aecia/aiiy oeio G-a?eea, ui aeeeeea? i?eai?/aiiy ICa i?e aeoeaaoe??
ionea?eiiaeo ?aoeaioi??a, aeei?enoiaoaaany eieethoiee oienei, yeee
naeaeoeaii ?iaeoeao? G-a?eee n?iaenoa Gi/Go (Katada & Ui, 1982),
?ic’?aeioth/e ?o ca’ycie ?c ?aoeaioi?ii. Eieethoiee oienei aeieoaaa IEAO
? ia aieeaaa ia aiie?ooaeo ICa o eiio?ie?, oiaoi o a?aenooiino? EO (?en.
14). O 23 ee?oeiao ICa o eiio?ieuei?e a?oi? aoa 474±48 iA (n =11), a
i?ney ia?iaee ee?oei oieneiii aiie?ooaea ICa neeaaeaea 384±55 iA
(P>0,2). Aiie?ooaea IEAO i?e aie?eaoe?? EO (50 I) o oeeo ee?oeiao aoea
776±154 iA (n=11) ? 29±12 iA, a?aeiia?aeii (P<0,0001). I?e aie?eaoe?? EO i?eai?/aiiy ICa o ee?oeiao, ia?iaeaieo eieethoiei oieneiii, aoei a?aenooi?i aai cia/ii iaioei (?en. 14). O eiio?ie? aoaeo neeaaeaa 61,9±10,2 % (n=11), a i?ney ia?iaee oieneiii - 8,9±2,2 % (n=12) (P<0,0001). C iaoith ii??aiyeueii? oa?aeoa?enoeee IEAO aei??thaaany i?e i?aeo?eioaaiiio iioaioe?ae? 50 iA, i?e yeiio Ca2+ eaiaee aeaaeoeaiaai?, a ICa aei??thaaany i?ae /an ei?ioeeo ?iioeuen?a aei 0 iA, ui a?aeiia?aea? Erev IEAO. O oaeee niin?a aeinyaaeiny iaae?eia ?icae?eaiiy aeine?aeaeoaaieo no?oi?a. Aac o?enaoe?? ??aiy [Ca2+]i aie?eaoe?y EO aeeeeeaea iaeii/anii i?eai?/aiiy ICa ? aaia?aoe?th IEAO. Iaeaeaa aoaeoe ca oaeeo oiia aoee aeaioacieie. Ii/aoeiaa oaeaeea oaca a?eueoi? aiie?ooaee i/aaeaeii aoea iaoiiaeaia aea?eueiaiiyi Ca2+ ?c N?, ui aeeeeeaei Ca2+-caeaaeio ?iaeoeaaoe?th Ca2+ eaiae?a (Ganitkevich et al., 1987) ? aeiaeaoeiao aeoeaaoe?th eao?iiieo eaiae?a (Inoue & Isenberg, 1990). E??i oiai, oaea ii/aoeiaa i?aeaeuaiiy Ca2+ iaei cia/aiiy ? aeey ianooiiiai noaoe?iia?iiai i?eai?/aiiy ICa. Oae, o aeaieo aenia?eiaioao noaoe?iia?ia i?eai?/aiiy i?e ia?o?e aie?eaoe?? EO neeaaeaei 50±10 % (n=5), oiae? ye i?e o?enaoe?? [Ca2+]i ia ??ai? 100 iI ? i?e an?o ?ioeo ??aieo oiiaao ICa ciaiooaaany ia 27±4 % (n=14) (P<0,02). Ii/aoeiaa oaca aoea a?aenooiy a aenia?eiaioao, o yeeo [Ca2+]i o?enoaaany ia ??ai? 100 iI ?c aeei?enoaiiyi 10 iI BAPTA (?en. 14). Niinoa??aaeiny aeae?eueea ?noioieo ?icoiaeaeaiue o e?iaoeoe? oeeo aeaio a?aeiia?aeae. Ii-ia?oa, IEAO aeinyaaa iaeneioio cae/aeii /a?ac 5-10 n, oiae? ye ICa i?iaeiaaeoaaa ciaiooaaoeny i?ioyaii 1 oaeeeie. Ii-ae?oaa, o i?enooiino? EO IEAO aeanaineoecoaaany (0 iI AOO o i?iaooe?), a ICa caeeoaany ia oiio ae ??ai?. Ii-o?ao?, i?ney a?aeieaaiiy EO IEAO aeaaeoeaoaaany i?ioyaii aeae?eueeio naeoiae, oiae? ye a?aeiiaeaiiy ICa aeiaaaei i?eiaeii? 2-3 oaeeei. Oea iiaei na?ae/eoe i?i o/anoue ??cieo G-a?ee?a aai, ca oiiae o/ano? o a?aeiia?ae? oiai naiiai i?aeoeio ionea?eiiaiai ?aoeaioi?a ? G a?eea, i?i ?noioi? ?icoiaeaeaiiy o /ooeeaino? aei aeoeaiaaieo noaiaeeieoeue G-a?ee?a. C iaoith c'ynoaaiiy oeeo ieoaiue aoee i?iaaaeai? aenia?eiaioe c iiaoi?ieie aie?eaoe?yie aaii?noa ? ii??aiyiiy aoaeo?a aac AOO ? i?e aeiaeaaaii? 1 iI AOO aai AAeOS aei i?iaoi/iiai ?ic/eio. O i?enooiino? AOO iaeaeaa oeia a?aeiia?aeae aoee noaa?euei? o /an?. Aac aeiaeaaaiiy AOO niinoa??aaeany oaeaeea aeanaineoecaoe?y IEAO, aea ia i?eai?/aiiy ICa. ?acoeueoaoe aenia?eiaio?a c aeiaeaaaiiyi AAeOS oaae ni?aiaaeaee c oyaeaiiyie i?i ??cieoeth o /ooeeaino? aei aeoeaiaaieo G-a?ee?a - aaia?aoe?y IEAO iiai?noth aeieoaaeany i?e 1 iI AAeOS, oiae? ye aoaeo i?eai?/aiiy ICa cieeaa eeoa i?e 5 iI AAeOS. Ine?eueee oei ionea?eiiaiai ?aoeaioi?a, ui aeoeao? IEAO, aoa aecia/aiee, caaea/a eiai ?aeaioeo?eaoe?? aeey aoaeoo EO ia ICa caiaeeeany aei ii??aiyeueiiai aiae?co ae?? ionea?eiiaeo aioaaii?no?a ia IEAO ? ICa. O oeeo aenia?eiaioao aeei?enoiaoaaeeny I2 naeaeoeai? aioaaii?noe a?iaaoeei ? iaoieo?ai?i, a oaeiae I3 naeaeoeaiee aioaaii?no 4-DAMP. Ii??aiyiiy aoaeo?a aeey 10 aeine?aeaeoaaieo ee?oei i?e ia?aeaeuei?e ?a?no?aoe?? IEAO ? ICa aeaei i?aeoe/ii ?aeaioe/i? ?acoeueoaoe. Oea aeicaieyei c?iaeoe aeniiaie, ui, ye ? o aeiaaeeo aeoeaaoe?? IEAO, i?eai?/aiiy ICa aeeeeea?oueny aeoeaaoe??th I2 ?aoeaioi??a. Oeae aeniiaie oaeiae oe?eeii ocaiaeaeo?oueny c /ooeea?noth iaio a?aeiia?aeae aei ae?? eieethoiiai oieneio, ine?eueee oeae oienei ia aieeaa? ia G-a?eee, ui aeoeaothoueny I3 ?aoeaioi?aie. AIAE?C ? OCAAAEUeIAIIss ?ACOEUeOAO?A AeINE?AeAEAIUe Aoeaoeeoie?i - oea iniiaiee caoaeaeoth/ee iae?iia?aaeao/ee, ca o/anoth yeiai cae?enith?oueny ia?aneiiaoe/iee eiio?ieue nei?i/oaaeueii? aeoeaiino? on?o a?noea?aeueieo ? aeayeeo noaeeiieo aeaaeaiueeeo i'yc?a. A inoaii? ?iee ?ioa?an aei aea/aiiy iaoai?ci?a ae?? aoeaoeeoie?io cia/ii c??n, ui iaoiiaeaii aeae?eueeiia i?e/eiaie. C'ynoaaeiny, ui ionea?eiia? ?aoeaioi?e iaeaaeaoue aei n?iaenoaa 7-OI ?aoeaioi??a, ye? ia?aaeathoue neaiae ca o/anoth G-a?ee?a. Oea i?eionea? iiaeeea?noue a?eueo neeaaeieo i?eioeei?a ?aaoeyoe?? o ii??aiyii? c ?iiio?iiieie ?aoeaioi?aie, aea ?iiiee eaiae ? ?ioaa?aeueiith /anoeiith iieaeoee ?aoeaioi?a. E??i oiai, ionea?eiia? ?aoeaioi?e i?aeoe/ii o an?o aeine?aeaeaieo oeiao aeaaeaiueeeo i'yc?a aeyaeeeny aaoa?iaaiieie, a iniiaiiio i?aaenoaaeaieie i?aeoeiaie I2 ? I3. O ca'yceo c oeei aeieeioea iaiao?aei?noue aecia/aiiy ooieoe?? eiaeiiai c i?aeoei?a ?aoeaioi?a. Noaaaei oaeiae i/aaeaeiei, ui oie?ia?a?/ia aeoeaaoe?y - oea iaaecae/aeii neeaaeiee i?ioean c iaeii/aniei caeo/aiiyi aaaaoueio aoaeoi??a (?iii? eaiaee, aiceie, aoi?eii? iina?aaeieee). Ia?aeiiee neaiae a?ae aeoeaiaaieo aaii?noii ?aoeaioi??a iiaea aeey ??cieo aoaeoi??a iineethaaoeny aai iineaaeyoeny ca ?aooiie cai?ioieo ca'yce?a. E??i oiai, iaeii/ania aeoeaaoe?y aeaio oei?a ?aoeaioi??a caeo/a? ??ci? eeane G-a?ee?a (ye i?aaeei, Gq/11 aeey I3 ? Gi/Go aeey I2 ?aoeaioi?a) ?c ??ciith niaoeeo?/i?noth noiniaii oeo aai ?ioei aoaeoi??a. I?e an?e neeaaeiino? oeyo?a ? iaoai?ci?a ia?aaea/? neaiaeo, iiaeia oiaaiaii noaa?aeaeoaaoe, ui a iniia? oie?ia?a?/iiai caoaeaeaiiy ? nei?i/aiiy eaaeaoue aeaiiey?ecaoe?y iaia?aie, ao?ae Ca2+ o ee?oeio ? aea?eueiaiiy Ca2+ ?c aioo??oiueiee?oeiieo aeaii. A?aeiia?aeii, o aeai?e ?iaio? iniiaia oaaaa i?eae?eyeany aeine?aeaeaiith iaoai?ci?a aeoeaaoe?? eao?iiii? i?ia?aeiino? iaia?aie ? oie?ia?a?/iiai eiio?ieth Ca2+ eaiae?a, a oaeiae iaoai?ci?a aea?eueiaiiy Ca2+. sse ia?aaeoiiaa, aeaeo?io?c?ieia?/iee aiae?c caoaeaeoth/i? ae?? aoeaoeeoie?io i?a caniiaoaaoeny o?eueee ia aeaoaeueiiio aea/aii? ? ?icoi?ii? aeanoeainoae ?iiieo eaiae?a iaia?aie AIE. Aoee aeyaeai? cia/i? aeaeia? ? a?eia? iniaeeaino? a aeni?an?? oeo aai ?ioeo ?iiieo eaiae?a o AIE eeoa/ieeo. Ao?aeiee no?oi i?a ia?aiineoeny ye /a?ac iioaioe?aeea?iaai? Ca2+, oae ? OOO-/ooeea? Na+ eaiaee. E??i oiai, o eoeueoeaiaaieo AIE eeoa/ieeo ethaeeie i?e ianeaiiio aeniaaeaii? aioo??oiueiee?oeiieo Ca2+ aeaii aeieeaa ao?aeiee no?oi, iiae?aiee aei ICRAC o iacaoaeeeaeo ee?oeiao. A AIE ICRAC ?ai?oa ia aoa ca?a?no?iaaiee. O AIE ileum ii?nueei? naeiee Na+ eaiaee a?aenooi?, oiio i?e oie?ia?a?/i?e aeaiiey?ecaoe?? a?aee?eaathoueny o?eueee Ca2+ eaiaee L-oeio. Aiie ae, i/aaeaeii, aeeiiothoue ? iniiaio ?ieue i?aeo?eiee ??aiy Ca2+ o aioo??oiueiee?oeiieo caianieeao. K+ eaiaee a AIE eeoa/ieeo i?aaenoaaeai? a iniiaiiio eaiaeaie aeo?aeiiai aei?yieaiiy, a AIE ileum uo?a aeii?ioth/ei aeyaeany eiiiiiaio oaeaeeiai aeo?aeiiai oieo (IA), a a AIE ileum ii?nueei? naeiee - Ca2+-caeaaeiee eiiiiiaio. Inoaii?e aeia?a ei?aeth? ?c ci?iith [Ca2+]i ? aeeiio? aaaeeeao ?ieue ?aiiey?ecaoe?? iaia?aie ye i?e aaia?aoe?? iioaioe?ae?a ae??, oae ? aeey iaiaaeaiiy ? i?eieiaiiy oie?ia?a?/ii? aeaiiey?ecaoe??. Aeaeo?e/ia aeoeai?noue i?aioa?aeueieo iae?ii?a oaeiae aoiaeeea a eiei aeine?aeaeoaaieo i?iaeai, oiio ui naia aiia ? o??th ii/aoeiaith eaieith, ui i?eaiaeeoue aei ca?eueiaiiy aoeaoeeoie?io e ?ioeo ia?aaeao/ee?a o ia?aiaeo cae?i/aiiyo, ye? ?aaoeththoue nei?i/oaaeueio aeoeai?noue AIE. ?iii? no?oie a oeeo iae?iiao aoee aeine?aeaeai? iaaeinoaoiuei. Iniaeeaee ?ioa?an i?aaenoaaeyee aeanoeaino? IK,ir. Aeine?aeaeaiiy oeueiai no?oio aaaeeeaa aeey ?icoi?iiy i?e?iaee o?eaaei? ne?aeiai? a?ia?iiey?ecaoe??, oa?aeoa?ii? aeey iae?ii?a AH/oei 2. Iiae?? ia iaia?ai? ? ona?aaeei? AIE, ui ianooiathoue i?ney io?eiaiiy ee?oeiith oie?ia?a?/iiai noeioeo a?ae iae?iia, eia?/ii i?inoaaeeoe o iine?aeiaiino? a?ae aeoeaaoe?? ?aoeaioi?a aei i?aeaeuaiiy [Ca2+]i, ye iieacaii ia ocaaaeueithth/ee noai? ia ?en. 15. Aca?iiae?y aoeaoeeoie?io c ionea?eiiaeie I2 ?aoeaioi?aie i?ecaiaeeoue ca aeiiiiiaith aeoeaaoe?? /ooeeaeo aei eieethoiiai oieneio Gi/Go a?ee?a aei a?aee?eaaiiy eao?iiieo eaiae?a, /ei iaoiiaeaia iniiaia caoaeaeoth/a ae?y. Aaaeeeai a?aecia/eoe, ui ?ai?oa ?ieue I2 ?aoeaioi??a aaaaeaeany iai?yiith ? caiaeeeany aei aioaaii?cio aeoeaaoe?? aae?aii?aoeaioi??a oeyoii i?eai?/aiiy aaeaiae?eoeeeeace ? cieaeaiiy ??aiy oeAIO. ?ieue I2 ?aoeaioi??a o a?noea?aeueieo AIE aeeneooo?oueny aeaaii, a ?o aaeeea e?euee?noue (a?ey 80%) aac aecia/aii? i?yii? ooieoe?? aaaaeaeany ia?aaeienii. Ne?ae cacia/eoe ? oa, ui ileum ii?nueei? naeiee aaaaea?oueny eeane/iei “I3-naeaeoeaiui“ i?aia?aoii, ui oe?iei aeei?enoiao?oueny o oa?iaeieia?/ieo aeine?aeaeaiiyo. C'yniaoaaiiy i?yii? ?ie? a?eueoino? I2 ?aoeaioi??a o oe?e oeaiei? ciooo? ia?aaeyiooe oae? oyaeaiiy. Ae?oaith ooieoe??th I2 ?aoeaioi??a ? i?eai?/aiiy aoiaeo Ca2+ /a?ac eaiaee L-oeio. Ia ia?oee iiaeyae iiaea iieacaoeny, ui oaea ae?y noia?a/eoue caaaeueiiio caoaeaeoth/iio aoaeoo, aea oea iiaea aeeiioaaoe aaaeeeao ?ieue iaiaaeaiiy aoiaeo Ca2+ i?e oie?ia?a?/i?e aeaiiey?ecaoe??. I?e aoiae? Ca2+ aeeth/athoueny aeae?eueea iaoai?ci?a, ui iineeththoue neaiae - E?AE ? ii/aoeiaa iineeaiiy ??AE, a c?inoaiiy [Ca2+]i i?aeneeth? aeoeaaoe?th eao?iiieo eaiae?a, ui i?ecaiaeeoue aei iineeaiiy aeaiiey?ecaoe?? ? ua a?eueoiio ca?eueoaiith aoiaeo Ca2+ (?en. 15). E??i oiai, aeaiiey?ecaoe?y ca?eueoo? ye ?i eao?iiiiai eaiaeo, oae ? /ooeea?noue aei aaii?noo. Oaeei /eiii, o aeai?e neeaaei?e nenoai? ? aeae?eueea iiceoeaieo cai?ioieo ca'yce?a, ui aa?aioothoue ?icaeoie aeaiiey?ecaoe??, a nai oa?aeoa? iioaioe?aecaeaaeiino? IEAO aecia/a? ?? ?aaaia?aoeaiee oa?aeoa?. Iaoai?cie, ui iaiaaeothoue aeoeaaoe?th, ia iano?eueee aaaaoi/enaeuei? - oea a iniiaiiio ?icaeoie IK(Ca) ? cao?eiaia ?iaeoeaaoe?y ??AE. Aeanaineoecaoe?y IEAO, i/aaeaeii, a?ae?a?a? iaaio ?ieue, aea o ii??aiyii? c ?ioeie i?ioeanaie aiia ?icaeaa?oueny iaaaaaoi iia?euei?oa, iniaeeai i?e iayaiino? aeinoaoiuei? e?eueeino? AOO. A??ia?aeii, ui i?e aaaaoueio iaoieia?/ieo noaiao, iia'ycaieo ?c i?aeaeuaiith /ooeea?noth aei oie?ia?a?/ii? noeioeyoe??, ii?ooothoueny naia i?ioeane aaeueioaaiiy. I?eai?/aiiy ICa oaeei /eiii iiaeia aaaaeaoe aaaeeeaei ?aaoeyoi?iei iaoai?ciii. Oe?eaai i?e oeueiio a?aecia/eoe, ui i?e ni?eueiino? ioneiaeo eaiie (I2-Gi/Go) e?iaoeea IEAO ? i?eai?/aiiy ICa ?noioii ??ciyoueny. Inoaii?e ?icaeaa?oueny iia?euei?oa ? o?eaa? i?ney a?aeieaaiiy aaii?noa iaaaaaoi aeiaoa, ye ae aeath/e oei naiei i?iyaeoeny caoaeaeaiith, a iio?i eiai i?eieieoe. Oaea iiaeoeyoe?y ICa iiaea aooe iia'ycaiith c o/anoth iia?eueiiai aioo??oiueiee?oeiiiai iina?aaeieea, yeee iiee ia ?aeaioeo?eiaaii. Aaaeeeai a?aecia/eoe, ui aeyaeai? i?eioeeie ?aaoeyoe?? eao?iiiiai eaiaeo i?eioneathoue, ca aiaeia??th c aeoeaaoe??th, ?aaaia?aoeaiee oa?aeoa? aeaaeoeaaoe??. sseui ii/aeany a?ia?iiey?ecaoe?y iaia?aie, ciaioaiiy aoiaeo Ca2+, iioaioe?aecaeaaeia aeaaeoeaaoe?y eaiaeo a?aeiia?aeii aei e?eai? Aieueoeiaia, cieaeaiiy /ooeeaino? aei aaii?noo ? iaio o?niee ca'ycie c aeoeaiaaieie G-a?eeaie ? oeie oaeoi?aie, ui aoaeooue i?enei?thaaoe cae?eaaiiy eao?iiieo eaiae?a. ?aaoeyoe?y aeoeaiino? eao?iiiiai eaiaeo ia? ae?aaeaiee eiiiiiaio, iia'ycaiee ?c eiioeaio?aoe??th aeoeaiaaieo G-a?ee?a o ee?oei?. C'ynoaaeiny, ui aeoeaiaai? G-a?eee i?e aca?iiae?? c eaiaeii ia i?inoi eiai a?aee?eaathoue, a aeeiiothoue aeoeaio ?ieue iiaeoeyoe?? aeanoeainoae eaiaeo. I?e oeueiio a?aeaoaa?oueny aaeeeee, ia aeanyoee i?e?aieueo, cnoa e?eai? aeoeaaoe?? oa?e a?ae’?iieo iioaioe?ae?a i?e i?aeaeuaii? eiioeaio?aoe?? aaii?noo ? oa?e iiceoeaieo iioaioe?ae?a i?e aeanaineoecaoe??. I?e oeueiio nooo?ai ci?iththoueny ye oi?ia noaoe?iia?ii? aieueoaiia?ii? caeaaeiino?, oae ? e?iaoeea no?oio, a cai?iiiiiaaia iiaeaeue aeicaieeee iiynieoe oe? ci?ie ye iio?aei? a?ae ia?aeiiiai iniiaiiai i?ioeano ci?ie ae?aiaciio iioaioe?ae?a aeoeaaoe?? i?ia?aeiino?. Ia cae?i/aiiy iiaeia a?aecia/eoe, ui c?noaaeaiiy io?eiaieo ?acoeueoao?a c aeaieie e?oa?aoo?e aeicaiey? aeyaeoe caaaeuei? caeiiii??iino? ?aaoeyoe?? ?iiieo eaiae?a o iaia?ai? AIE i?e aeoeaaoe?? ionea?eiiaeo ?aoeaioi??a. ?iie Ca2+, ye? aea?eueiythoueny i?e aeoeaaoe?? nenoaie I3/Gq/11/ oinoie?iaca N, aeoeaothoue eao?iii?, Cl- ? AENa eaiaee ? ?iaeoeaothoue Ca2+ eaiaee. I2 ?aoeaioi?e iiaeoeththoue aeoeai?noue eaiae?a aaciina?aaeiuei, ?c caeo/aiiyi G-a?ee?a, /ooeeaeo aei eieethoiiai oieneio (a??ia?aeii Gi/Go). Oea i?ecaiaeeoue aei a?aee?eaaiiy eao?iiieo eaiae?a, i?eai?/aiiy AENa eaiae?a ? iiaeoeyoe?? aeoeaiino? Ca2+ eaiae?a. AENIIAEE 1. C aeei?enoaiiyi iaoiaeeee patch-clamp ?a?no?aoe?? ?ioaa?aeueieo no?oi?a ? no?oi?a /a?ac iiiaeeiie? ?iii? eaiaee aoee aeine?aeaeai? iniiai? eaiee o neeaaei?e iine?aeiaiino? iiae?e, ui a?aeaoaathoueny i?e I-oie?ia?a?/i?e aeoeaaoe?? AIE oiieiai eeoa/ieeo. 2. Caoaeaeoth/a ae?y aoeaoeeoie?io iiina?aaeeiaaia aieiaiei /eiii eiai aca?iiae??th c I2 ?aoeaioi?aie, ui oeyoii aeoeaaoe?? /ooeeaeo aei eieethoiiai oieneio (EO) G-a?ee?a i?ecaiaeeoue aei a?aee?eaaiiy eao?iiieo eaiae?a. I3 ?aoeaioi?e aecia/athoue iaeneiaeueia /enei aeoeaieo eaiae?a. 3. Ao?ae Ca2+ /a?ac eaiaee L-oeio i?ecaiaeeoue aei ?aaaia?aoeaiiai Ca2+-?iaeoeiaaiiai aea?eueiaiiy Ca2+ ?c aioo??oiueiee?oeiieo aeaii, ca ?aooiie /iai Ca2+ neaiae cia/ii iiaeiaaeo?oueny. I?aeaeuaiiy [Ca2+]i aeeeeea? ii/aoeiaa iineeaiiy ? cao?eiaia i?eai?/aiiy InsP3-?iaeoeiaaiiai aea?eueiaiiy Ca2+. Oeei aecia/a?oueny aeieeiaiiy inoeeeyoe?e [Ca2+]i ? eao?iiiiai no?oio i?e aeoeaaoe?? ionea?eiiaeo ?aoeaioi??a. Aeiaeaoeiaee ??aaiue ?aaoeyoe?? Ca2+-caeaaeieo i?ioean?a aeeth/a? i?eai?/aiiy Ca2+ no?oio, iiina?aaeeiaaia aeoeaaoe??th I2 ?aoeaioi??a ? /ooeeaeo aei EO G-a?ee?a. 4. Aeaiaaeaioi? eao?iie ? i?ioiie iiaeoeththoue eao?iiio i?ia?aei?noue, i?ioa ?? iioaioe?aecaeaaei?noue ia iia'ycaia c iiaeeeaei iioaioe?aecaeaaeiei aeieoaaiiyi Ca2+, Mg2+ aai I+. 5. Aeine?aeaeaiiy aeanoeainoae eao?iiieo eaiae?a iieacaei, ui iniiaiei ? eaiae ?c i?ia?aei?noth a?ey 40 iN. A??ia?aei?noue eiai ciaoiaeaeaiiy o a?aee?eoiio noai? cieaeo?oueny i?e a?ia?iiey?ecaoe?? iaia?aie aiane?aeie ciaioaiiy /ano aeeooy o a?aee?eoiio noai? ? cia/iiio ca?eueoaii? /ano aeeooy o cae?eoiio noai?. 6. I?e aca?iiae?? aeoeaiaaieo G-a?ee?a ?c eao?iiieie eaiaeaie a?aeaoaa?oueny cia/ia iiaeoeyoe?y ?o iioaioe?aecaeaaeieo aeanoeainoae. Aeoeaaoe?eia e?eaa ci?uo?oueny ia?aeaeueiei /eiii ia aeanyoee i?e?aieueo a iaeanoue iaaaoeaieo iioaioe?ae?a i?e i?aeaeuaii? eiioeaio?aoe?? aeoeaiaaieo G-a?ee?a ? o i?ioeeaaeiiio iai?yi? i?e aeanaineoecaoe??. Inoaii?e i?ioean ? AOO-caeaaeiei. Cnoa aeoeaaoe?eii? e?eai? a on?o aeiaaeeao noi?iaiaeaeo?oueny ?noioieie ci?iaie e?iaoeee ?aeaenaoe?? no?oio. 7. Cnoa aaee/eie V1/2 iiynith? iioaioe?aecaeaaei?noue iniiaieo e?iaoe/ieo oac eao?iiiiai no?oio, a naia: eaoaioiiai ia??iaeo, oaeaeeinoae aeoeaaoe??, aeanaineoecaoe?? ? aeaaeoeaaoe??, a oaeiae oaiiiai iiaea?eiiai (?aiiueiai ? i?ciueiai) “ia?aoeiaiiy” aiie?ooae no?oio i?e ??cieo iioaioe?aeao. 8. Oie?ia?a?/ia aeoeaaoe?y AIE ? neeaaeiei aeeiai?/iei i?ioeanii, a yeiio ??aaiue iaia?aiiiai iioaioe?aeo, aioo??oiueiee?oeiiiai Ca2+ ? eiioeaio?aoe?y aeoeaiaaieo G-a?ee?a ? iniiaieie aca?iiae?th/eie oaeoi?aie. 9. I?aeoe/ia cia/aiiy ?iaioe caeeth/a?oueny o anoaiiaeaii? ooieoe?iiaeueii? ?ie? I2 oeio oie?ii?aoeaioi??a ? neeueii? iioaioe?aecaeaaeiino? /ooeeaino? aei aaii?noo (20-e?aoia ciaioaiiy AN50 i?e aeaiiey?ecaoe?? ia 100 iA), ui aa?oi a?aoiaoaaoe i?e e?eoaaii? ??ciiiai?oieo caoai?thaaiue, iaoiiaeaieo i?aeaeuaiith ?aaeoeai?noth aei oie?ia?a?/ieo noeioe?a. ?iaioe, a yeeo iioae?eiaai? iaoa??aee aeena?oaoe??: 1. Aaeaeai E.A., AEiein A.A. Aiaiei - aunieiniaoeeoe/aneee e yooaeoeaiue aeieaoi? iaeioi?uo eaeueoeeecaaeneiuo eaeeaauo i?iaiaeeiinoae // Iae?ioeceieiaey. - 1988. - 20, ?6. - N.833846. 2. AEiein A.A., Aaeaeai E.A. O/anoea aioo?eeeaoi/iiai eaeueoeey a aeoeaaoeee eaeueoeeecaaeneiuo eaeeaauo oieia a eciee?iaaiiuo eeaoeao eeoa/ieea ii?neie naeiee // Aeieiae/aneea iaia?aiu. - 1989. - 6, ?4. - N. 431-433. 3. Ooaa I.O., AEiein A.A., Aaeaeai E.A. Oaiaoathuaa aeaenoaea eioaeia ia iioaioeeaeicaaeneiue eaeueoeeaaue oie eciee?iaaiiuo aeaaeeiiuoa/iuo eeaoie eeoa/ieea // Aeieeaaeu Aeaaeaiee iaoe NNN?. - 1989. - 309, ?1. - N. 240-243. 4. AEiein A.A., Aaeaeai E.A., Ooaa I.O. Eaeeaaue oie a iaia?aia eciee?iaaiiie aeaaeeiiuoa/iie eeaoee, aeoeae?oaiue i?e aunaiaiaeaeaiee eaeueoeey ec aioo?eeeaoi/iuo aeaii // Aeieiae/aneea iaia?aiu. - 1990. - 7, ?3. - N. 306-316. 5. Ooaa I.O., AEiein A.A., Aaeaeai E.A. Aeaenoaea aeoeaaoi?ia e aeieaoi?ia aunaiaiaeaeaiey Na2+ ec aioo?eeeaoi/iuo aeaii ia o?ainiaia?aiiua eiiiua oiee eciee?iaaiiie aeaaeeiiuoa/iie eeaoee // Aeieiae/aneea iaia?aiu. - 1990. - 7, ?3. - N. 317-325. 6. Zholos A.V., Baidan L.V., Shuba M.F. Inhibitory action of caffeine on calcium current in intestinal isolated smooth muscle cell // Pflgers Archiv. - 1991. - 419. - P. 267-273. 7. Zholos A.V., Baidan L.V., Shuba M.F. Properties of the late transient outward current in isolated intestinal smooth muscle cell of the guinea-pig // Journal of Physiology. - 1991. - 443. - P. 555-574. 8. AEiein A.A., Ooaa I.O. ?aaaia?aoeaiia eaeueoeeeeiaeooee?oaiia aunaiaiaeaeaiea eaeueoeey ec aioo?eeeaoi/iuo aeaii aeaaeeiiuoa/iie eeaoee // Aeieeaaeu Aeaaeaiee iaoe NNN?. - 1991. - 317, ?3. - N. 735-738. 9. Zholos A.V., Baidan L.V., Shuba M.F. Some properties of Ca2+-induced Ca2+ release mechanism in single visceral smooth muscle cell of the guinea-pig // Journal of Physiology. - 1992. - 457. - P. 1-25. 10. Smirnov S.V., Zholos A.V., Shuba M.F. Potential-dependent inward currents in single isolated smooth muscle cells of the rat ileum // Journal of Physiology. - 1992. - 454. - P. 549-571. 11. Smirnov S.V., Zholos A.V., Shuba M.F. A potential-dependent fast outward current in single smooth muscle cells isolated from the newborn rat ileum // Journal of Physiology. - 1992. - 454. - P. 573-589. 12. Baidan L.V., Zholos A.V., Shuba M.F., Wood J.D. Patch clamp recording in myenteric neurons of guinea-pig small intestine // American Journal of Physiology. - 1992. - 262. - P. G1074-G1078. 13. Zholos A.V., Bolton T.B. G-protein control of voltage-dependence as well as gating of muscarinic metabotropic channels in guinea-pig ileum // Journal of Physiology. - 1994. - 478. - P. 195-202. 14. Zholos A.V., Komori S., Ohashi H., Bolton T.B. Ca2+ inhibition of inositol trisphosphate-induced Ca2+ release in single smooth muscle cells of guinea-pig small intestine // Journal of Physiology. - 1994. - 481. - P. 97-109. 15. Zholos A.V., Bolton T.B. Effects of divalent cations on muscarinic receptor cationic current in smooth muscle from guinea-pig small intestine // Journal of Physiology. - 1995. - 486. - P. 67-82. 16. Baidan L.V., Zholos A.V., Wood J.D. Modulation of calcium currents by G-proteins and adenosine in myenteric neurones cultured from adult guinea-pig small intestine // British Journal of Pharmacology. - 1995. - 116. - P. 1882-1886. 17. Zholos A.V., Bolton T.B. (1996). Properties of the muscarinic cationic channel in longitudinal smooth muscle of guinea-pig small intestine // Smooth Muscle Excitation. - London: Academic Press. - 1996. - P. 155-173. 18. Zholos A.V., Bolton T.B. A novel GTP-dependent mechanism of ileal muscarinic metabotropic channel desensitization // British Journal of Pharmacology. - 1996. - 119. - P. 997-1005. 19. Zholos A.V., Bolton T.B. Effects of protons on muscarinic receptor cationic current in single visceral smooth muscle cells // American Journal of Physiology. - 1997. - 272. - P. G215-G223. 20. Bolton T.B., Zholos A.V. Activation of M2 muscarinic receptors in guinea-pig ileum opens cationic channels modulated by M3 muscarinic receptors // Life Sciences. - 1997. - 60. - P. 1121-1128. 21. Zholos A.V., Bolton T.B. Muscarinic receptor subtypes controlling the cationic current in guinea-pig ileal smooth muscle // British Journal of Pharmacology. - 1997. - 122. - P. 885-893. 22. Pucovsky V., Zholos A.V., Bolton T.B. Muscarinic cation current and suppression of Ca2+ current in guinea pig ileal smooth muscle cells // European Journal of Pharmacology. - 1998. - 346. - P.323-330. 23. Zholos A.V. Muscarinic effects on ion channels in smooth muscle // Neurophysiology. - 1999. - 31 (3). - C. 212-228. 24. Zholos A.V. Modulation of the voltage operating range of ion channels: theoretical considerations and experimental studies // Aeiiia?ae? Aeaaeai?? iaoe Oe?a?ie. - 1999. - 8. - C. 170-175. 25. Bolton T.B., Prestwich S.A., Zholos A.V. & Gordienko D.V. (1999). Excitation-contraction coupling in gastrointestinal and other smooth muscles // Annual Reviews in Physiology. - 1999. - 61. - P. 85115. 26. AEiein A.A. Iioaioeee?othuaa aeaenoaea Na2+ ia eiiceoie 1,4,5-o?enoinoao-eiaeooee?oaiia aunaiaiaeaeaiea Na2+ a aeaaeeiiuoa/iuo eeaoeao oiieiai eeoa/ieea ii?neie naeiee // Oeceea aeeaiai. - 1999. - 7(1). - N. 59-69. 27. Zholos A.V., Baidan L.V., Starodub A.M. & Wood J.D. Potassium channels of myenteric neurons in guinea-pig small intestine // Neuroscience. - 1999. - 89(2). - P. 603-618. AEiein I.A. Iaia?aii? oa aioo??oiueiee?oeii? iaoai?cie I-oie?ia?a?/ii? aeoeaaoe?? aeaaeaiueeii’yciaeo ee?oei oiieiai eeoa/ieeo. - ?oeiien. Aeena?oaoe?y ia caeiaoooy iaoeiaiai nooiaiy aeieoi?a a?ieia?/ieo iaoe ca niaoe?aeuei?noth 03.00.02 - a?io?ceea. - ?inoeooo o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie, Ee?a, 1999. C aeei?enoaiiyi iaoiae?a o?enaoe?? iioaioe?aeo, aioo??oiueiee?oeiii? ia?ooc?? ? oioie?co “caged” ?a/iaei aeine?aeaeoaaeeny iaoai?cie aeaiiey?ecaoe?? iaia?aie ? i?aeaeuaiiy aioo??oiueiee?oeiii? eiioeaio?aoe?? Ca2+ o i?ioean? ni?yaeaiiy caoaeaeaiiy ? nei?i/aiiy i?e oie?ia?a?/i?e aeoeaaoe?? aeaaeaiueeii’yciaeo ee?oei oiieiai eeoa/ieeo. Aeyaeaii nooo?a? aeaeia? ? a?eia? iniaeeaino? a aeni?an?? ? aeanoeainoyo ??cieo ?iiieo eaiae?a, a oaeiae aeaia oa?aeoa?enoeea ?iiieo no?oi?a o iaia?ai? iae?ii?a i?aei’yciaiai ieaoeaa. Iaae?ei?noue a?aeiia?ae? ee?oeie i?e aeoeaaoe?? ionea?eiiaeo oie?ii?aoeaioi??a caaacia/o?oueny aca?iiae??th aeae?eueeio i?ioean?a. Aeaiiey?ecaoe?y iaia?aie aiane?aeie aeoeaaoe?? eao?iiieo eaiae?a (I2 aoaeo) aeeeeea? ao?ae Ca2+ /a?ac eaiaee L-oeio, ui ?i?oe?th? Ca2+-?iaeoeiaaia aea?eueiaiiy Ca2+ ?c aioo??oiueiee?oeiieo aeaii. Oea noi?iaiaeaeo?oueny aeiaeaoeiaith Ca2+-caeaaeiith aeoeaaoe??th eao?iiieo eaiae?a ? ii/aoeiaei iineeaiiyi InsP3-?iaeoeiaaiiai aea?eueiaiiy Ca2+. ?icaeoie aeaiiey?ecaoe?? iaia?aie aeiaeaoeiai aeoeao? eao?iii? eaiaee aiane?aeie ciaioaiiy /ano ?o aeeooy a cae?eoiio noai? ? ca?eueoaiiy - o a?aee?eoiio noai?, a oaeiae oeyoii i?aeaeuaiiy /ooeeaino? aei aaii?noo. Caoeni? i?ioeane ? aeaaeoeaaoe?y caaacia/othoueny AOO-caeaaeiith aeanaineoecaoe??th eao?iiii? i?ia?aeiino?, i?eai?/aiiyi Ca2+ no?oio (I2 aoaeo), cao?eiaiith o?eaaeith Ca2+-caeaaeiith ?iaeoeaaoe??th InsP3 ?aoeaioi??a ? aeoeaaoe??th a?ia?iiey?ecoth/iai IK(Ca). Ae?aiacii aeoeaaoe?? eao?iiieo eaiae?a aeeiai?/ii i?iy?oueny o caeaaeiino? a?ae ??aiy aeoeaiaaieo G-a?ee?a. Ia oe?e i?aenoaa? cai?iiiiiaaia iiaeaeue aaia?aoe?? eao?iiiiai no?oio, yea iiynith? eiai e?iaoe/i? ? iioaioe?aecaeaaei? aeanoeaino?. Eeth/ia? neiaa: aeaaeaiueeii’ycia? ee?oeie, aoeaoeeoie?i, ionea?eiia? ?aoeaioi?e, G-a?eee, eao?iiiee no?oi, Ca2+ no?oi, Ca2+- ? InsP3-?iaeoeiaaia aea?eueiaiiy Ca2+, aeanaineoecaoe?y. AEiein A.A. Iaia?aiiua e aioo?eeeaoi/iua iaoaieciu I-oieeia?ae/aneie aeoeaaoeee aeaaeeiiuoa/iuo eeaoie oiieiai eeoa/ieea. - ?oeiienue. Aeenna?oaoeey ia nieneaiea o/aiie noaiaie aeieoi?a aeieiae/aneeo iaoe ii niaoeeaeueiinoe 03.00.02 - aeioeceea. - Einoeooo oeceieiaee ei. A.A. Aiaiiieueoea IAI Oe?aeiu, Eeaa, 1999. N eniieueciaaieai iaoiaeia oeenaoeee iioaioeeaea, aioo?eeeaoi/iie ia?oocee e oioieeca “caged” aauanoa enneaaeiaaeenue iaoaieciu aeaiiey?ecaoeee iaia?aiu e iiauoaiey aioo?eeeaoi/iie eiioeaio?aoeee Ca2+ a i?ioeanna nii?yaeaiey aicaoaeaeaiey e nie?auaiey i?e oieeia?ae/aneie aeoeaaoeee aeaaeeiiuoa/iuo eeaoie oiieiai eeoa/ieea. Iaia?oaeaiu nouanoaaiiua aeaeiaua e aic?anoiua iniaaiiinoe a yeni?annee e naienoaao ?acee/iuo eiiiuo eaiaeia, a oaeaea aeaia oa?aeoa?enoeea eiiiuo oieia a iaia?aia iae?iiia iaaeiuoa/iiai nieaoaiey. Iaaeaaeiinoue ioaaoa eeaoee i?e aeoeaaoeee ionea?eiiauo oieeii?aoeaioi?ia iaania/eaaaony acaeiiaeaenoaeai ianeieueeeo i?ioeannia. Aeaiiey?ecaoeey iaia?aiu aneaaenoaea aeoeaaoeee eaoeiiiuo eaiaeia (I2 yooaeo) aucuaaao aoiae Ca2+ /a?ac eaiaeu L-oeia, eioi?ue eieoeee?oao Ca2+-eiaeooee?oaiia aunaiaiaeaeaiea Ca2+ ec aioo?eeeaoi/iuo aeaii. Yoi nii?iaiaeaeaaony aeiiieieoaeueiie Ca2+-caaeneiie aeoeaaoeeae eaoeiiiuo eaiaeia e ia/aeueiui oneeaieai InsP3-eiaeooee?oaiiai aunaiaiaeaeaiey Ca2+. ?acaeoea aeaiiey?ecaoeee iaia?aiu ieacuaaao aeiiieieoaeueiue aeoeae?othuee yooaeo ia eaoeiiiua eaiaeu aneaaenoaea oei?i/aiey a?aiaie eo aeecie a cae?uoii ninoiyiee e oaaee/aiey - a ioe?uoii ninoiyiee, a oaeaea iooai iiauoaiey /oanoaeoaeueiinoe e aaiienoo. Caueoiua i?ioeannu e aeaaeoeaaoeey iaania/eaathony AOO-caaeneiie aeanaineoecaoeeae eaoeiiiie i?iaiaeeiinoe, oaiaoaieai Ca2+ oiea (I2 yooaeo), caaea?aeaiiie aeeeoaeueiie Ca2+-caaeneiie eiaeoeaaoeeae InsP3 ?aoeaioi?ia e aeoeaaoeeae aeia?iiey?ecothuaai IK(Ca). Aeeaiacii aeoeaaoeee eaoeiiiuo eaiaeia iiaeaa?aeai neiaeiui aeeiaie/iui eciaiaieyi a caaeneiinoe io o?iaiy aeoeae?iaaiiuo G-aaeeia. Ia yoii iniiaaiee i?aaeeiaeaia iiaeaeue aaia?aoeee eaoeiiiiai oiea, iauyniythuay aai eeiaoe/aneea e iioaioeeaecaaeneiua naienoaa. Eeth/aaua neiaa: aeaaeeiiuoa/iua eeaoee, aoeaoeeoieei, ionea?eiiaua ?aoeaioi?u, G-aaeee, eaoeiiiue oie, Ca2+ oie, Ca2+- e InsP3-eiaeooee?oaiia aunaiaiaeaeaiea Ca2+, aeanaineoecaoeey. Zholos A.V. Membrane and intracellular mechanisms of the M-cholinergic activation of smooth muscle cells from the small intestine. - Manuscript. Thesis for a doctor’s degree by speciality 03.00.02 - biophysics. - A.A. Bogomoletz Institute of Physiology of National Academy of Sciences of Ukraine, Kyiv, 1999. The mechanisms underlying membrane depolarization and intracellular Ca2+ rise during cholinergic excitation-contraction coupling in intestinal smooth muscle cells were studied by use of patch-clamp techniques and flash photolysis of various “caged” substances. Important species- and age-related differences in the expression and properties of various ion channels have been found in non-stimulated cells. Ionic currents in myenteric neurones have also been characterised. Reliable cell response following muscarinic acetylcholine receptors stimulation occurs as a result of the interaction of several processes. Membrane depolarization due to cationic channel opening (M2 receptor-mediated) evokes Ca2+ entry via L-type channels which initiates Ca2+-induced Ca2+ release from the intracellular store. This in turn produces an additional Ca2+-dependent activation of the cationic channels and an initial augmentation of the InsP3-induced Ca2+ release. Developing depolarization further activates cationic channels due to the closed state shortening and the open state prolongation, as well as by sensitizing the cell to the agonist. Protective processes and deactivation involve GTP-dependent desensitization of the cationic conductance, Ca2+ current inhibition (an M2 effect), delayed long-lasting Ca2+-dependent inactivation of the InsP3 receptors and hyperpolarizing IK(Ca) activation. The voltage range of cationic channel activation is dynamically altered depending on the level of activated G proteins. On the basis of these observations a mathematical model of the muscarinic receptor-gated cationic current generation is presented which explains its kinetics and voltage-dependent properties. Key words: smooth muscle cells, acetylcholine, muscarinic receptors, G-proteins, cationic current, Ca2+ current, Ca2+- and InsP3-induced Ca2+ release, desensitization.

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