Роль потенціал-керованих кальцієвих каналів в гальмівній синаптичній передачі культивованих нейронів гіпокампу щурів: Автореф. дис… канд. біол. наук

Iaoe?iiaeueia Aeaaeai?y Iaoe Oe?a?ie

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

?na?aa Ieaia Aaeaioei?aia

OAeE 612.822

?ieue iioaioe?ae-ea?iaaieo eaeueoe??aeo eaiae?a

a aaeuei?ai?e neiaioe/i?e ia?aaea/? eoeueoeaiaaieo iae?ii?a a?iieaiio
uo??a.

03.00.13- o?c?ieia?y ethaeeie oa oaa?ei

Aaoi?aoa?ao aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa a?ieia?/ieo iaoe

Ee?a-1999 ?.

Aeena?oaoe??th ? ?oeiien

?iaioa aeeiiaia a ?inoeooo? o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie

Iaoeiaee ea??aiee:

Aeieoi? a?ieia?/ieo iaoe Aanaeianueeee Ieeiea Na?a?eiae/ 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

Io?oe?ei? iiiiaioe:

Aeaaeai?e IAI Oe?a?ie, aeieoi? a?ieia?/ieo iaoe, caa. a?aeae?eii
o?ceei-o?i?/ii? a?ieia?? ee?oeiieo iaia?ai ?inoeoooo o?c?ieia?? ?i. I.I.
Aiaiiieueoey IAI Oe?a?ie E?eooaeue Ieaa Ieaenaiae?iae/

Aeieoi? iaaee/ieo iaoe, ea??aiee Oeaio?o aeiee?i?/iiai aea/aiiy
e?ea?nueeeo cania?a Oa?iaeieia?/iiai eii?oaoo IIC Oe?a?ie Nieiaeia
Aiaoie?e ?aaiiae/

I?ia?aeia onoaiiaa ?inoeooo aa?aioieia?? AII Oe?a?ie, i.Ee?a

Caoeno a?aeaoaeaoueny “ 8 ” /a?aiy 1999 ?. i 14-00 aiaeei? ia can?aeai?
niaoe?ae?ciaaii? a/aii? ?aaee Ae-26.198.01 i?e ?inoeooo? o?c?ieia?? ?i.
I.I. Aiaiiieueoey IAI

Oe?a?ie, i. Ee?a, aoe. Aiaiiieueoey, 4.

C aeena?oaoe??th iiaeia iciaeiieoenue o a?ae?ioaoe? ?inoeoooo o?c?ieia??
?i. I.I. Aiaiiieueoey,i. Ee?a, aoe. Aiaiiieueoey, 4.

Aaoi?aoa?ao ?ic?neaiee » 23 » ea?oiy 1999 ?.

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

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

Caaaeueia oa?aeoa?enoeea ?iaioe

Aeooaeuei?noue i?iaeaie. Ca?aeii c no/anieie oyaeaiiyie, a iniia?
neeaaeii? ooieoe?iiaeueii? i?aai?caoe?? oeaio?aeueii? ia?aiai? nenoaie
eaaeeoue oiiea aca?iiae?y i?ae aeaiia iniiaieie i?ioeanaie —
caoaeaeaiiyi oa aaeueioaaiiyi. sse caoaeaeaiiy, oae ? aaeueioaaiiy o
OeIN caaacia/o?oueny o?i?/ieie iae?iia?aaeao/eeaie (iaae?aoi?aie),
caeaoieie aca?iiae?yoe c a?aeiia?aeieie ?aoeaioi?ieie ooai?aiiyie
iae?iiaeueieo iaia?ai. Noai iaae?aoi?ieo i?ioean?a, iino?eia aca?iiae?y
i?ae ieie ia? i?eioeeiiaa cia/aiiy aeey ii?iaeueiiai ooieoe?iioaaiiy
iiceo.

O o?c?ieia?? cae?eniaiiy neiaioe/ii? ia?aaea/? iae?ii?a oeaio?aeueii?
ia?aiai? nenoaie ?nio? aaeeea e?euee?noue ia?ica’ycaieo ieoaiue, ui
noinothoueny eiio?ieth aea?eueiaiiy iae?iiaae?aoi?a iiina?aaeeiaaiiai
aoiaeii ?ii?a Na2+ o i?aneiaioe/ia cae?i/aiiy /a?ac iioaioe?ae-ea?iaai?
eaeueoe??a? eaiaee. Ine?eueee i?aneiaioe/i? ia?aia? cae?i/aiiy
a?eueoino? iae?iiaeueieo oei?a ee?oei ? iaaeinyaeieie aeey i?yieo
aeaeo?io?c?ieia?/ieo aeine?aeaeaiue, a?io?ce/i? aeanoeaino? eaeueoe??aeo
eaiae?a, eieae?ciaaieo o i?aneiaioe/ieo oa?i?iaeyo, aea/ai? o?eueee ia
iaaaeeei? e?eueeino? ia’?eo?a aaco?aaaoieo (Edmonds et al., 1990;
Augustine et al., 1987) oa o?aaaoieo (Lemos and Nowycky, 1989; Yawo,
1990; Stanley and Goping, 1991). Aeey ?aeaioeo?eaoe?? ??ciiiai?oieo
oei?a eaeueoe??aeo eaiae?a, ye? iiina?aaeeiaothoue neiaioe/io ia?aaea/o,
iaea?eueo /anoi aeei?enoiaothoue oa?iaeieia?/iee i?aeo?ae (Taschenberger
et al., 1995; Wheeler et al., 1994; Akaike, 1997). A?eueo?noue
aeine?aeaeaiue o oe?e aaeoc? i?enay/aii caoaeaeoth/?e neiaioe/i?e
ia?aaea/?, oiae? ye o/anoue eaeueoe??aeo eaiae?a a aaeuei?ai?e
neiaioe/i?e ia?aaea/? aea/aia ia aeinoaoiuei. A inoaii?e /an noaei
a?aeiii, ui ye aeey ??ciiiai?oieo oei?a iae?ii?a, oae ? a iaaeao iaei???
? o??? ae iiioeyoe?? ia?aiaeo ee?oei, aea?eueiaiiy iaeiiai ? oiai ae
iaae?aoi?a iiaea eiio?iethaaoeny ??ciiiai?oieie oeiaie eaeueoe??aeo
eaiae?a. O?c?ieia?/ia ?ieue oaeiai ??ciiiai?ooy ua ia aei e?ioey
aeyaeaia. Oey ianoaaeia, ii?yae c iaeaaaeeea?oith ?ieeth neiaioe/ieo
i?ioean?a o /eneaiieo o?c?ieia?/ieo ?aaeoe?yo i?aai?cio coiiaeth?
iaiao?aei?noue ?aoaeueiiai aeine?aeaeaiiy caaaeueieo aeanoeainoae
neiaioe/ii? ia?aaea/?, ?? iaoai?cio oa iiooeo cania?a aea??eiaiai
oa?iaeieia?/iiai aieeao ia i?ioeane, ye? eaaeaoue a ?? iniia?.

Iiaeaeueiei ia’?eoii aeey iaoeo aeine?aeaeaiue aoea ia?aia ia?aeiia
eoeueoo?a iaei? u?eueiino? iae?ii?a a?iieaiio uo??a. Oaea iiaeaeue aeey
aeine?aeaeaiiy aaeuei?aii? neiaioe/ii? ia?aaea/? ia? aaaaoi ia?aaaa:
i?enooi?noue ?ioa?iae?ii?a (aaeuei?aieo i?aneiaioe/ieo ee?oei) oa
i??ai?aeieo iae?ii?a (iinoneiaioe/ieo ee?oei) a eoeueoo?? oa
iiaeeea?noue aeine?aeaeaiiiy aaeuei?aii? neiaioe/ii? ia?aaea/?
?iaeea?aeoaeueii? ia?e iae?ii?a, iiaeeea?noue eieaeueii? noeioeyoe??
iiiaeeiaeiai iae?eoa (aeniia) oa eieaeueii? ia?ooc?? ia iaiaaeaio
ieiueio, o yeo aoiaeeea o?eueee ia?a iae?ii?a, ui aeine?aeaeoaaeanue.
A?eueo oiai, ia iaia?ai? aaeuei?aieo iae?ii?a a?iieaiio aoea aeyaeaia
iaeii/ania iayai?noue aeae?eueeio oei?a iioaioe?ae-ea?iaaieo
eaeueoe??aeo eaiae?a (Lambert and Wilson, 1996), ui aea? iiaeeea?noue
aeine?aeaeaiiy o/ano? ??cieo oei?a eaeueoe??aeo eaiae?a a aaeuei?ai?e
neiaioe/i?e ia?aaea/?.

Iaoa ? caaea/? aeine?aeaeaiiy. Iaoith aeaii? ?iaioe aoei aeine?aeaeaiiy
aeeeeeaieo aaeuei?aieo iinoneiaioe/ieo no?oi?a (aAINN) o i?ioean?
?icaeoeo eoeueoo?e iae?ii?a a?iieaiio uo??a, aea/aiiy ?oi?o iniiaieo
yeaeo?io?ce/ieo oa oa?iaeieia?/ieo oa?aeoa?enoee, a oaeiae c’ynoaaiiy
?ie? ??ciiiai?oieo iioaioe?ae-ea?iaaieo eaeueoe??aeo eaiae?a o
aaeuei?ai?e neiaioe/i?e ia?aaea/?.

Caaea/?:

1. C aeei?enoaiiyi iaoiaeeee “iao/-eeaii” o eiio?ao?aoe?? “oe?ea
ee?oeia” ? caniao i?yii? iicaee?oeiii? noeioeyoe?? iae?eo?a aea/eoe
aeanoeaino? aaeuei?aieo iinoneiaioe/ieo no?oi?a a i?ioean? ?icaeoeo
iae?ii?a in vitro.

2. ?aeaioeo?eoaaoe oeie iioaioe?ae-ea?iaaieo eaeueoe??aeo eaiae?a, ui
eaaeaoue a iniia? eaeueoe??ai? i?ia?aei?no? iae?ii?a a?iieaiio.

3. Aeine?aeeoe o/anoue iioaioe?ae-ea?iaaieo eaeueoe??aeo eaiae?a o
aaeuei?ai?e neiaioe/i?e ia?aaea/?.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a. ?a?no?aoe?y e?iaoe/ieo
oa?aeoa?enoee ?iieo no?oi?a oa noaoenoe/iee aiae?c oeoeooaoe?e AINN ia
??cieo aoaiao eoeueoeaoaaiiy aeicaieeee i?inoaaeeoe aeeiai?eo ?icaeoeo
aaeuei?aieo neiaioe/ieo ca’yce?a in vitro. Aeine?aeaeaii aieea
??ciiiai?oieo aeieaoi??a eaeueoe??ai? i?ia?aeiino? ia aaeuei?aio
neiaioe/io ia?aaea/o. Aia?oa iieacaii, ui ieoaae?i?i aeieo? neiaioe/io
ia?aaea/o.

Oai?aoe/ia oa i?aeoe/ia cia/aiiy iaea?aeaieo ?acoeueoao?a. ?iaioa ia?
ia?aaeon?i ooiaeaiaioaeueiee ?ioa?an, ine?eueee aeicaiey? aeeaoa
c?icoi?oe caeiiii??iino?, ui eaaeaoue a iniia? ooai?aiiy neiaioe/ieo
ca’yce?a i?ae iae?iiaie a ia??iae ?aiiueiai iioiaaiaca. Io?eiai?
?acoeueoaoe oaeiae aeicaieythoue ?noioii iioe?eoe oyaeaiiy i?i ?ieue
??ciiiai?oieo iioaioe?ae-ea?iaaieo eaeueoe??aeo eaiae?a o aaeuei?ai?e
neiaioe/i?e ia?aaea/?. Iia? aeai? c oeueiai ieoaiiy ? aaaeeeaeie o ieai?
oi?ioaaiiy a?eueo iiaiiai oyaeaiiy i?i iaoai?ci, ui eaaeeoue a iniia?
i?aeee?oeiii? eiioi?eaoe??. ?acoeueoaoe aeine?aeaeaiue aeacothoue oaeiae
ia iaiao?aei?noue o?aooaaiiy aieeao oa?iaeieia?/ieo i?aia?ao?a,
ni?yiiaaieo ia iiaeoeyoeeth eaeueoe??aeo no?oi?a, ia aaeuei?aio
neiaioe/io ia?aaea/o.

Iniaenoee aianie caeiaoaa/a. I?eaiooaaiiy eoeueoo?e iae?ii?a a?iieaiio
oa aenia?eiaioe ii aeine?aeaeaiith ?ie? iioaioe?ae-ea?iaaieo
eaeueoe??aeo eaiae?a o aaeuei?ai?e neiaioe/i?e ia?aaea/? aoee aeeiiaieie
aaoi?ii iniaenoi. Aenia?eiaioe ii aeine?aeaeaiith aeanoeainoae
aaeuei?aieo iinoneiaioe/ieo no?oi?a iae?ii?a o i?ioean? ?icaeoeo
eoeueoo?e iae?ii?a a?iieaiio i?iaiaeeeeny ni?eueii c ani. Neaei?aiei A.
A. O ?ic?iaoe? eiioeaioe?? ?iaioe aeoeaio o/anoue i?eeiaee ?io?
ni?aaaoi?e ae?oeiaaieo ?ia?o.

Ai?iaaoe?y ?acoeueoao?a aeena?oaoe??. Iniiai? iieiaeaiiy ?iaioe
aeeeaaeaeenue oa iaaiai?thaaeenue ia : OOVIII Annual Meeting of
Neuroscience Society (Los Angeles, 1998); International workshop
“Intracellular signaling” (Kiev, 1997); nai?ia?? ?i-oa O?c?ieia?? ?i. I.
I. Aiaiiieueoey (1998).

Ioae?eaoe??. Ca ?acoeueoaoaie ?iaioe iioae?eiaaii o?e noaoo? oa oace
aeaio aeiiia?aeae.

No?oeoo?a oa ianya aeena?oaoe??. Aeena?oaoe?y neeaaea?oueny c? anooio,
iaeyaeo e?oa?aoo?e, iaoa??ae?a oa iaoiae?a aeine?aeaeaiiy, ?acoeueoao?a
aeine?aeaeaiue, iaaiai?aiiy ?acoeueoao?a, aeniiae?a oa nieneo
aeei?enoaieo aeaea?ae c? 206 iaeiaioaaiue. ?iaioa aeeeaaeaia ia 104
noi??ieao oa ?ethno?iaaia 17 ?enoieaie.

Iniiaiee ci?no aeena?oaoe??

Iaoa??aee oa iaoiaee aeine?aeaeaiue.

I?eaiooaaiiy eoeueoo?e iae?ii?a a?iieaiio. Ia?aeiia eoeueoo?a iae?ii?a
a?iieaiio aoea io?eiaia a?ae iiaiia?iaeaeaieo uo??a e?i?? A?noa?. I?ney
ia?iaee 0,025%-oiei o??ineiii o aaceaeueoe??aiio oa aaciaai??aiio
?ic/ei? c oinoaoiei aooa?ii oeaieio a?iieaiio iaoai?/ii aeenia?aoaaee ca
aeiiiiiaith Ianoa?ianueeeo ieiaoie. Io?eiaio noniaic?th ee?oei
aenaaeaeoaaee c u?euei?noth 35000 iae./ni2 ia iie?eo? eai?i?iii oa
iie?-L-i?ieoeiii /aoee Iao??. Iae?iie ?inee oa ii?oieia?/ii
aeeoa?aioe?thaaeeny ai?iaeiaae aeaio oeaei?a a i?i?iaeuei?e na?aae? ?aea
c aeiaeaiiyi 10% e?iuenueei? ne?iaaoee, ?inoe?io (6 iea/ie) oa
aio?a?ioee?a i?e 370N o aoiinoa??, ui i?noeea 5% NI2. Ooieoe?iiaeuei?
ca’ycee i?ae iae?iiaie ooai?thaaeeny ia 4-6 aeaiue eoueoeaoaaiiy.

?a?no?aoe?y aeeeeeaieo aaeuei?aieo iinoneiaioe/ieo no?oi?a.
Aeaeo?io?c?ieia?/i? aeine?aeaeaiiy i?iaiaeeeeny ia 7, 11-14 ? 21 aeaiue
i?ney iinaaeee eoeueoo?e. Aeey ?a?no?aoe?? aaeuei?aieo iinoneiaioe/ieo
no?oi?a aeei?enoiaoaaeany iaoiaeeea “iao/-eeaii” o eiio?ao?aoe?? “oe?ea
ee?oeia”. Aaciaee ?ic/ei i?noea (o iI): NaCl — 140; KCl-3; CaC12 — 2;
MgCl2 — 2; HEPES — 20; aetheica — 30; pH=7,3. A iicaee?oeiiee ?ic/ei
aeiaeaaaeeny aeieaoi?e IIAeA oa iaIIAeA-?aoeaioi??a — DNQX oa D-APV o
e?eueeino? 20 ieI eiaeiee, ye? aeieoaaee caoaeaeoth/? iinoneiaioe/i?
no?oie. Aeey caiiaiaiiy “iao/-ieiaoee” (R=4-6MIi) aeei?enoiaoaaany
?ic/ei ianooiiiai neeaaeo (o iI): E-aetheiiao-100; KCl — 50; MgCl2 — 10;
EGTA — 10; HEPES — 20; pH=7,4. I?aeo?eioaaiee iioaioe?ae neeaaeaa -70
iA. Noeioeyoe?y i?aneiaioe/ii? ee?oee cae?enithaaeany iicaee?oeiii c
/anoioith 0,2 Aoe ca aeiiiiiaith neeyii? iee?iieiaoee i?eaeecii oiai ae
ae?aiao?o, ui ? “iao/-ieiaoea” (R= 2-4 IIi), caiiaiaii? iicaee?oeiiei
?ic/eiii. Iae?eo i?aneiaioe/ii? ee?oee iiae?acithaaany i?yiieooieie
?iioeuenaie no?oio o?eaae?noth 1 in oa aiie?ooaeith 0,05 — 1 ieA.

?a?no?aoe?y iioaioe?ae-ea?iaaieo eaeueoe??aeo no?oi?a. Aenia?eiaioe
i?iaiaeeeeny ia iae?iiao 10-12-oe aeaiii? eoeueoo?e. ?a?no?aoe?y
eaeueoe??aeo no?oi?a i?iaiaeeeany c aeiiiiiaith iaoiaeeee “iao/-eeaii” o
eiio?ao?aoe?? “oe?ea ee?oeia”. Iicaee?oeiiee ?ic/ei iaa oie naiee
neeaae, ui ? i?e ?a?no?aoe?? aAINN. Aeey i?eai?/aiiy
iioaioe?ae-ea?iaaieo iao???aeo eaiae?a o ?ic/ei aeiaeaaaany
oao?iaeioienei (OOO) o eiioeaio?aoe?? 1ieI. Aioo??oiueiieiaoi/iee ?ic/ei
iaa oaeee neeaae (o iI): NsCl — 130, OAA-Cl — 10, MgCl2 — 5, CaCl2 — 1,
AGOA- 10, Tris-Cl — 10; ?I aeiaiaeeee aei 7,3 aeiaeaaaiiyi NsII. Ii??
iao/-ieiaoee neeaaeaa 4-8 IIi. I?aeo?eioaaiee iioaioe?ae aa?ethaaa o
caeaaeiino? a?ae iaoe aenia?eiaioo. No?oie, ui ?a?no?oaaeenue,
o?eueo?oaaeenue c /anoioith c??co 5 eAoe oa ioeeo?iaoaaeenue ia /anoio?
1 eAoe. Iine?aeiaiee ii?? eiiiainoaaany aia?aoii ia 50-70 %.

Aie?eaoe?y aeieaoi??a AINN oa eaeueoe??aeo eaiae?a. Aeey ?aeaioeo?eaoe??
iinoneiaioe/ieo ?aoeaioi??a aeei?enoiaoany aeieaoi? AAIEA ?aoeaioi??a —
a?eoeoeei. Aeey oa?iaeieia?/iiai ?icae?eo eaeueoe??aeo no?oi?a
aeei?enoiaoaaeenue iai?aaie/iee aeieaoi? Nd2+, a oaeiae niaoeeo?/i?
i?aai?/i? aeieaoi?e aenieiii?iaiaeo eaeueoe??aeo eaiae?a: i?oaae?i?i —
aeieaoi? eaiae?a L-oeio, -CTx-GVIA (1ieI)- naeaeoeaiee aeieaoi? eaiae?a
N-oeio oa -Aga-IVA (200iI) — aeieaoi? eaiae?a ?-/ Q- oei?a. Aeieaoi?e
aie?eoaaeenue ia ieiuo 70-100 iei2 ca caniaii, yeee aoa iienaiee ?ai?oa
[Veselovsky et al., 1996 ].

Ia?iaea iaea?aeaieo ?acoeueoao?a. Ia/eneaiiy ia?aiao??a no?oi?a
ae?iaeyeiny i?ia?aiith Datasel ? AxoScop, a iiaeaeueoa iaoaiaoe/ia
ia?iaea aeaieo ? iiaoaeiaa ?enoie?a Origin ? PageMaker 6.5. Noaoenoe/ia
ia?iaea ?acoeueoao?a i?iaiaeeeany ca aeiiiiiaith i?ia?aie Origin.

?acoeueoaoe aeine?aeaeaiue.

E?iaoe/i? oa oa?iaeieia?/i? aeanoeaino? aeeeeeaieo aaeuei?aieo
iinoneiaioe/ieo no?oi?a. Aeine?aeaeaiiy aeanoeainoae aeeeeeaieo
aaeuei?aieo iinoneiaioe/ieo no?oi?a (aAINN), ui aeieeathoue ia
iinoneiaioe/i?e iaia?ai? i?e noeioeyoe?? i?aneiaioe/ii? ee?oeie, aoee
i?iaaaeai? ia iae?iiao eoeueoo?e iiiaae 14 aei?a in vitro.

I?e aie?eaoe?? 1ieM oao?iaeioieneia (TTX) iinoneiaioe/ia a?aeiia?aeue
iiai?noth oa cai?ioii aeieoaaeany, ui na?ae/eoue i?i oa, ui neiaioe/ia
ia?aaea/a, yea niinoa??aaeany a iaoeo aenia?eiaioao, aoea ?i?oe?eiaaia
iioaioe?aeii ae??, ui ?iaeooe?thaaany i?aneiaioe/iei noeioethaaiiyi
(?en.1A).

Aieueo-aiia?ia oa?aeoa?enoeea iinoneiaioe/iiai no?oio aoea e?i?eiith o
ae?aiacii? ci?ie i?aeo?eioaaiiai iioaioe?aeo a?ae -90 aei +20 iA
(?en.1A). Iioaioe?ae ?aaa?n?? aAINN (-14±5 iA), iaea?aeaiee
aenia?eiaioaeueiei oeyoii, iacia/ii a?ae??ciyany a?ae ??aiia?niiai
iioaioe?aeo aeey ?ii?a Cl-, ?ic?aoiaaiiai ii ??aiyiith Ia?inoa (-19 iA).

Aeeeeeai? AINN iaee iia?eueiee niaae, ui ai?ieneioaaany iaei??th
aeniiiaioith, c iino?eiith /ano 21±5 in.

I?eeeaaeaiiy a?eoeoeeia o eiioeaio?aoe?? 20 ieI aeeeeeaei iiaia
aeieoaaiiy aAINN (?en. 1A).

AAINN iae?ii?a o i?ioean? ?icaeoeo eoeueoo?e a?iieaiio uo??a. Aeey
ioe?iee caaaeueieo ci?i aaeuei?aii? neiaioe/ii? ia?aaea/? o i?ioean?
aeeoa?aioe?thaaiiy ee?oei no?oie, ui ?a?no?oaaeenue, ona?aaeithaaeenue
aeey eiaeii? a?eiai? a?oie ee?oie. Aoei anoaiiaeaii, ui na?aaeiy
aiie?ooaea aAINN aeinoia??ii ca?eueooaaeany c /anii eoeueoeaoaaiiy
iae?ii?a (?< 0,05) (?en.2A). A i?ioean? eoeueoeaoaaiiy iae?ii?a a?iieaiio niinoa??aaeiny ca?eueoaiiy ae?aiaciio aa??aaaeueiino? aiie?ooae aAINN (?en. 2A). sseui o iae?ii?a ia?oiai oeaeiy in vitro ?iceeae aiie?ooae no?oi?a neeaaeaa 60 - 230 iA, ae?oaiai oeaeiy - a?ae 100 aei 760 iA, oi o ee?oei o?aoueiai oeaeiy – a?ae 200 iA aei 1,6 iA. Aeey ioe?iee oeoeooaoe?e aiie?ooae aAINN ?ic?aoiaoaaeiny a?aeiinia na?aaei? a?aeoeeaiiy cia/aiue aiie?ooae no?oi?a, ui ?a?no?oaaeenue a?ae eiaeii? ia?e ee?oie, aeey ??cieo aoai?a eoeueoeaoaaiiy (O?aao, 1964). Noaoenoe/ii aeinoia??ii? ci?ie oe??? oa?aeoa?enoeee ia niinoa??aaeiny, ? aiia aa?ethaaea a iaaeao 16,5-18% (?en.2A) . O/anoue ?ii?a eaeueoe?y o aaeuei?ai?e neiaioe/i?e ia?aaea/?. E?eaa caeaaeiino? aiie?ooaee aAINN a?ae ??cieo eiioeaio?aoe?e iicaee?oeiiiai Ca2+ iienoaaeany ??aiyiiyi O?eea, yea caaacia/oaaei aaeaeaaoio ai?ieneiaoe?th aeaieo (?<0,05) c eiioeaio?aoe??th, i?e ye?e niinoa??aaeiny iieiaeiia aeieoaaiiy, 1,68 iI ? eiao?oe??ioii O?eea 2,64 (?en. 3). Iae?i?ei?noue a?aeiioaiiy i?ae eiioeaio?aoe??th iicaee?oeiiiai Ca2+ ? aiie?ooaeith aAINN aeaco? ia “eiiia?aoeaio” ae?th ?ii?a eaeueoe?y ia i?ioean aea?eueiaiiy iae?iiaae?aoi?a. Aeaa oeia eaeueoe??aeo no?oi?a o eoeueoeaiaaieo iae?iiao a?iieaiio. O a?eueoino? ee?oie o ?ic/ei?, yeee i?noea OOO, o a?aeiia?aeue ia no?ae/ano? aeaiiey?eco/? ci?uaiiy iaia?aiiai iioaioe?aeo a?ae i?aeo?eioaaiiai iioaioe?aeo -90 iA aeieeaa Ca2+ no?oi, yeee iaa ia aieueo-aiia?i?e oa?aeoa?enoeoe? aeaa oa?aeoa?ieo iaeneioie i?e -45±4 iA ? -17±6 iA, ye? a?aeiia?aeathoue iecueeiii?iaiaiio oa aenieiii?iaiaiio Ca2+ no?oiai (?en. 4). Ae?y iai?aai?/iiai aeieaoi?a eaeueoe??aeo eaiae?a Cd2+ ia aiie?ooaeo Ca2+ no?oi?a niie oa aAINN. Aeey aeine?aeaeaiiy iiaeeeai? ?ie? iecueeiii?iaiaiai eiiiiiaioo Ca2+ no?oio o aaeuei?ai?e neiaioe/i?e ia?aaea/? aeei?enoiaoaaany iai?aai?/iee aeieaoi? Ca2+ no?oi?a Cd2+. Ia ?en.5A iieacai? aieueo-aiia?i? oa?aeoa?enoeee Ca2+ no?oi?a a eiio?ie? oa i?ae aieeaii 10, 20 oa 50 ieM Cd2+. Oeiiaa ?a?no?aoe?y, ui iieaco? ciaioaiiy aiie?ooaee aAINN o ?acoeueoao? aie?eaoe?? 5 ieM Cd2+ i?aaenoaaeaia ia ?en 5A. Ia ?en. 5A iieacaii aeica-caeaaeia i?eai?/aiiy aiie?ooaee Ca2+ no?oi?a oa aAINN i?e i?eeeaaeaii? ??cieo eiioeaio?aoe?e Cd2+. Aeaeii, ui i?eeeaaeaiiy iaeeo eiioeaio?aoe?e oeueiai iai?aai?/iiai aeieaoi?a (10 ieM) aeeeeeaei neeueia ciaioaiiy aiie?ooaee aenieiii?iaiaeo Ca2+ no?oi?a oa aAINN, ? ia iaei aaaiiiai aoaeoo ia aiie?ooaeo iecueeiii?iaiaiai eiiiiiaioo Ca2+ no?oio. Ae?y i?aai?/ieo aeieaoi??a Ca2+ eaiae?a ia aiie?ooaeo aenieiii?iaiaiai Ca2+ no?oio oa aAINN. Aeine?aeaeaiiy oa?iaeieia?/ieo aeanoeainoae ??cieo eiiiiiaio?a aenieiii?iaiaiai Ca2+ no?oio i?iaiaeeeiny i?e ci?uaii? i?aeo?eioaaiiai iioaioe?aeo aei -60 iA aeey aeinyaiaiiy iiaii? noaoe?iia?ii? ?iaeo?aaoe?? iecueeiii?iaiaeo Ca2+ no?oi?a. Aeey oa?iaeieiae/iiai ?icae?eaiiy aenieiii?iaiaeo Ca2+ no?oi?a oa aeine?aeaeaiiy o/ano? ??cieo oei?a Ca2+ eaiae?a o aaeuei?ai?e neiaioe/i?e ia?aaea/? ie aeei?enoiaoaaee niaoeeo?/i? aeieaoi?e Ca2+ eaiae?a: i?oaae?i?i, -CTx-GVIA oa -Aga-IVA. Ia ?enoieo 6A iieacaia ae?y ??cieo eiioeaio?aoe?e i?oaae?i?ia ia aiie?ooaee Ca2+ no?oi?a oa aAINN. Aeaeii, ui i?oaae?i?i, ui ? niaoeeo?/iei aeieaoi?ii L-oeio Ca2+ eaiae?a o eiioeaio?aoe?? “iane/aiiy” - 10 ieM i?eai?/oaaa aiie?ooaeo aenieiii?iaiaiai Ca2+ no?oio ia 23±5 %. Aiie?ooaea aAINN i?e oeueiio ciaiooaaeany eeoa ia 4±6%. I?e aie?eaoe?? a?eueo aenieeo eiioeaio?aoe?e i?oaae?i?ia (50,100 ieM) aiie?ooaea aenieiii?iaiaiai Ca2+ no?oio aeieoaaeany ia 35±11 % oa 42±7 %, a aAINN ia 17±3 % oa 34±7 %, a?aeiia?aeii. (?en. 6A). Ai?ien?iaoe?y e?eai? aeica-aoaeo aieeao i?oaae?i?ia ia aiie?ooaeo Ca2+ no?oio oa aAINN ca aeiiiiiaith ??aiyiiy O?eea aoea noaoenoe/ii ia aeinoia??ia (p>0,05).

I?e aie?eaoe?? 1ieM -CTo-GVIA aiie?ooaea Ca2+ no?oio ciaiooaaeany ia 30
±5 %, a aAINN — ia 39±6 % (?en. 6A). Oe?eaai, ui aeieoaaiiy ye
aiie?ooaee aenieiii?iaiaiai Ca2+ no?oio, oae ? aAINN a ?acoeueoao?
ni?eueii? aie?eaoe?? 1ieM -CTo-GVIA ? 100 ieM i?oaae?i?ia aoea ieae/a,
i?ae aeaaa?a?/ia noia aeieo i?e aeiaeaoeo eiaeiiai aeieaoi?a ie?aii.
Oae, aeaaa?a?/ia noia aoaeo?a, i?e ie?aiiio i?eeeaaeaii? i?oaae?i?ia ?
-CTo-GVIA aoea ??aia i?eaeecii 72 % aeey aiie?ooaee Ca2+ no?oio ? 73 %
aeey aAINN, oi/a i?e ni?euei?e aie?eaoe?? oeeo aeaio i?aai?/ieo
aeieaoi??a aiie?ooaea Ca2+ no?oio i?eai?/oaaeany ia 56±12 %, a aAINN —
ia 49±3 % (?en. 6A).

I?e aie?eaoe?? -Aga-IVA (200iM) aiie?ooaea Ca2+ no?oio ? aAINN a
na?aaeiueiio ciaiooaaeany ia 37±13% ? 42 ±6 % (?en.6A).

Ni?eueia aie?eaoe?y i?oaae?i?ia (100 ieM), -CTo-GVIA (1ieM) oa -Aga-IVA
(200iM) aeeeeeaea ciaioaiiy aiie?ooaee Ca2+ no?oio ? aAINN ia 84±5 % ?
86±7 %, a?aeiia?aeii (?en. 6Ae). Ia ?en. 7 i?aaenoaaeaia ae?y ??cieo
i?aai?/ieo aeieaoi??a i?ioyaii iine?aeiaii? aie?eaoe?? ia aiie?ooaeo
aAINN iae?iia a?iieaiio ia 11 aeaiue in vitro.

Iaaiai?aiiy.

Aaeuei?ai? iinoneiaioe/i? no?oie a eoeueoeaiaaieo iae?iiao a?iieaiio.
No?oie, ui aeine?aeaeoaaeenue a iaoeo aenia?eiaioao, aoee
?aeaioeo?eiaai? ye oei?i? no?oie, ui aeieeathoue i?e aeoeaaoe??
AAIE-?aoeaioi??a oeio A, ca iioaioe?aeii ?aaa?n?? oa /ooeea?noth aei
niaoeeo?/iiai aeieaoi?a oeeo ?aoeaioi??a — a?eoeoeeio (Barker and Owen,
1986; Curtis, 1970).

A i?ioean? aea/aiiy aAINN a eoeueoo??, ui ?icaeaa?oueny, aoei aeyaeaia
ca?eueoaiiy na?aaeiuei? aiie?ooaee oa ae?aiaciia ?iceeaeo aiie?ooae
iinoneiaioe/ieo no?oi?a c? ca?eueoaiiyi a?eo eoeueoo?e. sse ca?eueoaiiy
na?aaei?o aiie?ooae no?oi?a, oae ? ca?eueoaiiy ?oiueiai ?iceeaeo c a?eii
iae?ii?a o eoeueoo?? iiaeia iiynieoe ca?eueoaiiyi e?eueeino? neiaioe/ieo
ca’yce?a i?ae ie?aieie iae?iiaie oa oneeaaeiaiiyi no?oeoo?e
iae?iiaeueiie ia?aae? a i?ioean? ?inoo ? aeeoa?aioee?iaee iae?ii?a a
eoeueoo?? (Kraszewski and Grantyn, 1992).

A iaoeo aeine?aeaeaiiyo aiie?ooaea an?o aAINN oeoeoothaaea, ye oea aoei
iienaii ? a iiia?aaei?o ?iaioao [Bekkers at al., 1990; Frerking et al.,
1995 ]. Oe? oeoeooaoe?? iiaeooue iiynithaaoeny i?eiaeii? aeaiia
i?e/eiaie: iaiaeii??aei?noth ?iciianthaeaeaiiy iioaioe?aeo ae?? ii
aeniio a neeo ??cieo eaaaeueieo aeanoeainoae ie?aieo eiai a?eie [Grantin
et al.,1983], aai eaaioiaeie aeanoeainoyie ie?aieo neiaioe/ieo eiioaeo?a
[Kettenmann et al.,1992]. A?aoiaoth/e oa, ui c a?eii eoeueoo?e nooo?ai
ci?ith?oueny a?o?oaeoii?ea ie?aieo iae?ii?a ? no?oeoo?a neiaioe/ieo
ca’yce?a i?ae ieie [Banker and Goslin,1991; Warton et al.,1990], iiaeia
aoei a i?eionoeoe, ui oea a?ae?a’?oueny a ci?i? aa??aaaeuei?no?
a?aeiia?aeae ie?aieo neiaioe/ieo ca’yce?a. I?ioa aiie?ooaee
iinoneiaioe/ii? a?aeiia?ae? aeey eiaeii? ie?aii? ia?e iae?ii?a iaee
iino?eiee ??aaiue oeoeooaoe?e ye i?e i?ino?e (iieiaea eoeueoo?a), oae ?
i?e neeaaei?e (aei?inea eoeueoo?a) ia?aia?e ia?aae?, yeee neeaaeaa a
na?aaeiueiio 17 %. Aeoiaey/e c? neacaiiai iiaeia aaaaeaoe, ui
oeoeooaoe?? aiie?ooae aAINN a eiaei?e ie?ai?e ?a?no?aoe?? a iaoeo
aenia?eiaioao aoee iaoiiaeai? i? iaiaeii??aei?noth ?iciianthaeaeaiiy
iioaioe?aeo ae??, a, ii an?e aeaeeiino?, eaaioiaeie aeanoeainoyie
ie?aieo neiaioe/ieo eiioaeo?a.

O/anoue ??cieo iioaioe?ae-ea?iaaieo Ca2+ eaiae?a o aaeuei?ai?e
neiaioe/i?e ia?aaea/?. Aeoiaey/e c iaea?aeaieo aeaieo, a niiaoe/i?e
iaia?ai? a?eueoino? iae?ii?a a?iieaiio ia 10-12 aeaiue eoeueoeaoaaiiy
aoee i?enooi? iecueeiii?iaiaee oa aenieiii?iaiaee eiiiiiaioe Ca2+
no?oio, ui a?aeiia?aea? iaea?aeaiei ?ai?oa aeaiei ia iae?iiao, ui
eoeueoeaoaaeenue, ? na?aei?cieueiaaieo iae?iiao a?iieaiio uo??a (Bley et
al., 1987; Yaary et al., 1987; Doerner et al., 1988; Meyers and Barker,
1989).

Aeey aeine?aeaeaiiy iiaeeeai? ?ie? iecueeiii?iaiaiai eiiiiiaioo Ca2+
no?oio o aaeuei?ai?e neiaioe/i?e ia?aaea/? aeei?enoiaoaaany iai?aai?/iee
aeieaoi? Ca2+ no?oi?a Cd2+. A?aeiii, ui eaaei?e o aenieeo
eiioeaio?aoe?yo ? ianaeaeoeaiei aeieaoi?ii Ca2+ eaiae?a, oiae? ye aei
iecueeeo eiioeaio?aoe?e eaaei?y iecueeiii?iaia? eaiaee iaio /ooeea?,
i?ae aenieiii?iaia? (Ozawa et al., 1989; Mogul and Fox., 1991).
I?eeeaaeaiiy iaeeo eiioeaio?aoeee oeueiai iai?aai?/iiai aeieaoi?o (10
ieM) aeeeeeaei nooo?aa ciaioaiiy aiie?ooaee aenieiii?iaiaeo Ca2+
no?oi?a ? aAINN, ? ia iaei ?noioiiai aoaeoo ia aiie?ooaeo
iecueeiii?iaiaiai eiiiiiaioo Ca2+ no?oio. Aeoiaey/e c oeeo aeaieo iiaeia
c?iaeoe aeniiaie, ui iecueeiii?iaia? Ca2+ eaiaee, iiaeeeai, ia aa?ooue
o/ano? o neiaioe/i?e ia?aaea/? a aeine?aeaeaieo iaie iae?iiao, ui
a?aeiia?aea? iaea?aeaiei ?ai?oa aeaiei ia iae?iiao oaeaiona uo??a ?
iae?iiao nieiaeueieo aaiae??a eo?/ao (Pfrieger et al., 1992; Holtz et
al., 1988). Oe?eaai, ui Eaiin e Iia?oee? (Lemos and Nowycky,1989) ia
aeyaeee iecueeiii?iaiaeo Ca2+ eaiae?a a i?aneiaioe/ieo oa?ieiaeyo
o?aaaoieo.

?niothoue /eneaii? aeine?aeaeaiiy, ye? i?aeoaa?aeaeothoue, ui aeae?eueea
oei?a aenieiii?iaiaeo Ca2+ no?oi?a, aeeth/ath/e N- ? P-/Q- oeie, aa?ooue
o/anoue a aea?eueiaii? iae?iiaae?aoi?a a aaeuei?aieo oa caoaeaeoth/eo
neiainao (Luebke et al., 1993; Wheeler et al., 1995; Scholz and Miller,
1995). Aenieiii?iaiaee Ca2+ no?oi niiaoe/ii? iaia?aie a iaoeo
aeine?aeaeaiiyo ca oa?iaeieia?/ieie aeanoeainoyie iiaeia aoei iiae?eeoe
ia i?oaae?i?i-, -CTx-GVIA-, -Aga-IVA — /ooeea? eiiiiiaioe ? ia/ooeeaee
aei oeeo aeieaoi??a eiiiiiaio Ca2+ no?oio.

Aeeaeae?iie?eaeei/ooeeaee Ca2+ no?oi ?ai?oa aoa iienaiee a ?iaioao ia
na?aei?cieueiaaieo iae?iiao a?iieaiio, c??cao ? eoeueoo?? aeniei?
u?eueiino? (Lambert and Wilson, 1995; Akaike et al., 1997). I?oaae?i?i a
iaeeo eiioeaio?aoe?yo 0,5-1 ieM aeieoaaa 30-60% L-oeio Ca2+ no?oi?a
iae?ii?a a?iieaiio, ui eoeueoeaoaaeeny (Meyers and Barker, 1989).
Ine?eueee a iaoeo aenia?eiaioao oaeiae aoa ca?a?no?iaaiee Ca2+ no?oi,
/ooeeaee aei iaaaeeeeo eiioeaio?aoe?e i?oaae?i?io, oi iiaeia
noaa?aeaeoaaoe, ui a aeine?aeaeaieo iae?iiao oaeiae aoa i?enooi?e L-oei
Ca2+ eaiae?a.

I?eeeaaeaiiy 10 ieI i?oaae?i?io (naeaeoeaia eiioeaio?aoe?y aeey L-oeio
Ca2+ eaiae?a) ia aeeeeeaei ?noioiiai aoaeoo ia aiie?ooaeo aAINN, ui
na?ae/eoue i?i oa, ui L-oei Ca2+ eaiae?a, iiaeeeai, ia aa?a o/ano? a
aaeuei?ai?e neiaioe/i?e ia?aaea/?. Iiae?ai? aeai? aoee iaea?aeai? aeey
caoaeaeoth/eo neiain?a iae?ii?a oaeaiona ? a?iieaiio ? aaeuei?aieo
neiain?a iae?ii?a aaiae??a n?oe?ae? (Pfrieger et al., 1992; Wheeler et
al., 1994; Taschenberger and Grantin, 1995).

A?aeiii, ui -CTx-GVIA ? niaoeeo?/iei aeieaoi?ii N-oeio iae?iiaeueieo
Ca2+ eaiae?a (Plummer et al., 1989). *a?ac oa, ui a ?ioaa?aeueiiio Ca2+
no?oi? aeine?aeaeaieo iae?ii?a aoa ca?a?no?iaaiee -CTx-GVIA-/ooeeaee
eiiiiiaio, iiaeia c?iaeoe aeniiaie, ui a oeeo iae?iiao aoa i?enooi?e
N-oei Ca2+ eaiae?a.

I?eeeaaeaiiy -CTx-GVIA a eiioeaio?aoe?? 1 ieM i?ecaiaeeei aei ciaioaiiy
aiie?ooaee aAINN i?eaeecii ia 30%, ui na?ae/eoue i?i ca’ycie N-oeio Ca2+
eaiae?a c neiaioe/iith ia?aaea/ath. ?acoeueoaoe iaoeo aeine?aeaeaiue
ocaiaeaeothoueny c aeaieie iaea?aeaieie ?ai?oa ia iae?iiao a?iieaiio,
aea -CTx-GVIA i?eai?/oaaa neiaioe/io ia?aaea/o a NA1 ? NA2 ?aa?iiao
a?iieaiio (Kamiya et al., 1988; Dutar et al., 1989; Horne and Kemp,
1991).

Aenieiii?iaiaee eiiiiiaio Ca2+ no?oio aoa /ooeeaee aei -Aga-IVA, oi/a
nooi?iue aeieoaaiiy Ca2+ no?oio oeei oieneiii iaaeoi aa?ethaaea.
I?enooi?noue oaeiai -Aga-IVA-/ooeeaiai eiiiiiaioo Ca2+ no?oio a iae?iiao
c??c?a a?iieaiio uo??a ?ai?oa aoea iieacaia a ?iaio? Aea?ea (Akaike et
al., 1997).

A iaoeo aeine?aeaeaiiyo iao?eaaea i?eeeaaeaiiy -Aga-IVA aeeeeeaei
neeueia ciaioaiiy aiie?ooaee aAINN. Oe? aeai? iiaiaeyoueny ?c ?ai?oa
iaea?aeaieie aeaieie, aea -Aga-IVA aeieoaaa caoaeaeoth/o neiaioe/io
ia?aaea/o a NA3-NA1 ?aa?iiao a?iieaiio ( Luebke et al., 1993; Takahashi
and Momiyama, 1993) oa ciaiooaaa ao?ae Ca2+ a neiaioiniie iiceo (Mintz
et al., 1992b; Geer et al., 1993). A iiia?aaei?o aeine?aeaeaiiyo aoei
iieacaii, ui aaeee? eiioeaio?aoe?? -Aga-IVA (200-800iI) ia aeieoaaee T-,
L- oa N-oeie Ca2+ eaiae?a neiiaoe/ieo iae?ii?a (Mintz and Bean, 1993).
-Aga-IVA-/ooeeaee eiiiiiaio Ca2+ no?oio a i?aneiaioe/ieo oa?ieiaeyo
iae?ii?a a?iieaiio (Wu and Saggau, 1994) ? a nii? iae?ii?a c ??cieo
a?aeae?e?a OeIN (Mintz et al., 1992a, b; Mintz and Bean, 1993) aoa
?aeaioeo?eiaaiee ye ?-oei Ca2+ no?oi?a. I?ioa, oaeiae aoei iieacaii, ui
aaeee? eiioeaio?aoe?? -Aga-IVA aeieoaaee Q-oei Ca2+ eaiae?a (Randall et
al., 1993; Sather et al., 1993). Oaeiae aoei aeneiaeaia i?eiouaiiy, ui
Q-oei Ca2+ eaiae?a iiaea ciaoiaeeoeny a i?aneiaioe/ieo oa?ieiaeyo
iae?ii?a NA1 ?aa?iio a?iieaiio uo??a (Randall et al., 1993). Ie ia
iiaeaii neacaoe, /e ? aeine?aeaeaiee iaie -Aga-IVA-/ooeeaee eiiiiiaio
Ca2+ no?oio ?-, Q-oeiii aai iaiia oeiaie Ca2+ no?oi?a, oiio
?aeaioeo?eoaaee Ca2+ no?oie, ui aeieothoueny oeei oieneiii, ye
-Aga-IVA-/ooeeaee eiiiiiaio Ca2+ no?oio.

A iaoeo aeine?aeaeaiiyo 16±5 % aiie?ooaee niiaoe/iiai Ca2+ no?oio ?
14±7% aAINN aoee ia /ooeeaeie aei aenieeo eiioeaio?aoe?e i?oaaeeieio,
-Aga-IVA oa -CTx-GVIA i?e ?oi?e ni?euei?e aie?eaoe??. O iaoeo
aeine?aeaeaiiyo ie aeei?enoiaoaaee aaeee? eiioeaio?aoe?? oeeo
i?aai?/ieo aeieaoi??a Na2+ eaiae?a, oiio ?acenoaioiee no?oi,
ii-aeaeeiiio, ia iiaeia a?aeianoe aei N -, L — ? P -/Q-oei?a Ca2+
no?oi?a, oi/a ie ia iiaeaii noaa?aeaeoaaoe oea iaiaaii. Iayai?noue
?acenoaioiiai no?oio iiaeia iiynieoe i?enooi?noth a iae?iiao a?iieaiio
Ca2+ eaiae?a R-oeio aai ?ioeo ia?aeaioeo?eiaaieo oei?a. Oe?eaai, ui
eiiiiiaio Ca2+ no?oio, ui ia aeieoaaany iaeii/aniith i?enooi?noth
aeieaoi??a L -, N -, P -Q — oei?a Ca2+ no?oi?a aoa ciaeaeaiee a iaia?ai?
iae?iiia ??cieo a?aeae?e?a OeIN, aeeth/ath/e iae?iie a?iieaiio [Akaike,
1997; Dolphin et al., 1993; Mintz et al., 1992a].

A?aeiii, ui i?oaae?i?i a eiioeaio?aoe?yo a?eueoa 10 ieM ianiaoeeo?/ii
aeieo? ??ci? oeie Ca2+ eaiae?a (Waard et al., 1996). sse aoei iieacaii
aeua, i?eeeaaeaiiy 50, 100 ieI i?oaae?i?io neeueii ciaiooaaei aiie?ooaeo
ye niiaoe/iiai aenieiii?iaiaiai Ca2+ no?oio, oae ? aiie?ooaeo aAINN.
E?ea? caeaaeiino? i?ae ??cieie eiioeaio?aoe?yie i?oaae?i?oeio ?
aiie?ooaeith Ca2+ no?oio ? AINN iiaaii ai?ieneioaaeenue ??aiyiiyi O?eea
(?>0,05), ui na?ae/eoue i?i oa, ui i?oaae?i?i a eiioeaio?aoe?yo, ui
canoiniaoaaeenue iaie, ianiaoeeoe/ii aeieoaaa Ca2+ no?oi. I?e ni?eueiiio
i?eeeaaeaii? i?oaae?i?io a eiioeaio?aoe?? 100 ieM ? -CTx-GVIA (1ieM)
aiie?ooaea aenieiii?iaiaiai Ca2+ no?oio ? aAINN aeieoaaeanue,
a?aeiia?aeii, ia 17% ? 23% iaioa, i?ae aeaaa?a?/ia noia on?aaeiaii? ae??
oeeo aeaio aeieaoi??a i?e ?o ie?aiiio i?eeeaaeaii?. Oaeei /eiii, iiaeia
c?iaeoe aeniiaie i?i oa, ui i?oaae?i?i o aaeeeeo eiioeaio?aoe?yo
ianaeaeoeaii i?eai?/oaaa w-CTx-GVIA-/ooeeaee eiiiiiaio Ca2+ no?oio.
A?eueo oiai, a iaoeo aenia?eiaioao caaaeaee aoa i?enooi?e eiiiiiaio Ca2+
no?oio, /ooeeaee aei aaeeeeo eiioeaio?aoe?e i?oaae?i?io ? ia/ooeeaee
aei -CTx-GVIA ? -Aga-IVA.

Iaea?aeai? aeai? na?ae/aoue i?i oa, ui aaeuei?aia neiaioe/ia ia?aaea/a a
iae?iiao a?iieaiio in vitro aieiaiei /eiii iiina?aaeeiao?oueny
aenieiii?iaiaeie Ca2+ no?oiaie, ui ca oa?iaeieia?/ieie aeanoeainoyie
iiaeia iiae?eeoe ia /ioe?e eiiiiiaioa: -CTx-GVIA- (N-oei), -Aga-?VA- (P
-Q-oeie) /ooeea? eiiiiiaioe, eiiiiiaio /ooeeaee aei aenieeo
eiioeaio?aoe?e i?oaae?i?io ? ia/ooeeaee aei oeeo i?aai?/ieo aeieaoi??a
eiiiiiaio Ca2+ no?oio.

Aeniiaee

1. Ia eoeueoo?? iecueei? u?eueiino? c aeei?enoaiiyi iaoiaeeee
«iao/-eeaii» a eiio?ao?aoe?? «oe?ea ee?oeia» ? iaoiaeo i?yii?
iicaee?oeiii? noeioeyoe?? aenii?a aea/ai? aeanoeaino? aaeuei?aieo
iinoneiaioe/ieo no?oi?a a i?ioean? ?icaeoeo iae?ii?a in vitro ? ?ieue
iioaioe?ae-ea?iaaieo eaeueoe??aeo eaiae?a a aaeuei?ai?e neiaioe/i?e
ia?aaea/? a neiaioe/iiio niieo/aii? i?ae aeaiia a?coaeueii
?aeaioeo?eiaaieie iae?iiaie a?iieaiio uo??a.

2. Anoaiiaeaii, ui ?c ca?eueoaiiyi o?eaaeino? eoeueoeaoaaiiy iae?ii?a
na?aaeiy aiie?ooaea aeeeeeaieo aaeuei?aieo iinoneiaioe/ieo no?oi?a oa
?oiy aiie?ooaeia aaoa?iaaii?noue noaoenoe/ii aeinoia??ii
ca?eueooaaeenue.

3. ?iceeae na?aaeiuei? aiie?ooaee no?oi?a, ui ?a?no?oaaeeny a?ae
iiiaeeiiei? ia?e iae?ii?a ? ? oa?aeoa?enoeeith aoaeoeaiino? neiaioe/ii?
ia?aaea/? i?ae aeaiia iae?iiaie, ia ci?ithaaany a i?ioean?
eoeueoeaoaaiiy.

4. Ia niiaoe/i?e iaia?ai? iae?ii?a a?iieaiio ia 10-12 aeaiue
eoeueoeaoaaiiy aeyaeaia i?enooi?noue aenieiii?iaiaiai ?
iecueeiii?iaiaiai eaeueoe??aeo no?oi?a. Aenia?eiaioe c i?aai?/ieie
aeieaoi?aie eaiae?a iieacaee, ui i?eiaeii? /ioe?e eiiiiiaioa
aenieiii?iaiaeo Ca2+ no?oi?a i?enooi? a a?eueoino? iae?ii?a
(aeeaeae?iie?eaeei-, -CTx-GVIA -, -Aga-IVA-/ooeea? oa ia/ooeeaee aei
oeeo aeieaoi??a eiiiiiaio).

5. Ia aeyaeaii o/ano? iecueeiii?iaiaeo eaeueoe??aeo no?oi?a o
aaeuei?ai?e neiaioe/i?e ia?aaea/? iae?ii?a, ui aeine?aeaeoaaeeny.

6. Iieacaii, ui aaeuei?aia neiaioe/ia ia?aaea/a a iae?iiao a?iieaiio in
vitro aieiaiei /eiii iiina?aaeeo?oueny aenieiii?iaiaeie Ca2+ eaiaeaie.
Ia iniia? /ooeeaino? aei niaoeeo?/ieo aeieaoi??a anoaiiaeaii, ui L-oei
eaeueoe??aeo no?oi?a (aeieoaaany 10 ieI ieoaae?i?io) ia ca’ycaiee c
aaeuei?aiith neiaioe/iith ia?aaea/ath, oiae? ye -CTx-GVIA (N-oei),
-Aga-?VA (P -Q-oeie) /ooeea? eiiiiiaioe, eiiiiiaio /ooeeaee aei aenieeo
eiioeaio?aoe?e i?oaae?i?io ? ia/ooeeaee aei oeeo i?aai?/ieo aeieaoi??a
eiiiiiaio Ca2+ no?oio aa?ooue o/anoue a aaeuei?ai?e neiaioe/i?e
ia?aaea/? iae?ii?a, ui aeine?aeaeoaaeeny.

Ia?ae?e iioae?eiaaieo i?aoeue caeiaoaa/a ca oaiith aeena?oaoe??.

Noaoo?:

1. Aaneeue?a Ae. B., Ina?aa I.A., Oaaeoeiaa N.A., Aanaeianueeee I.N.
I?aneiaioe/ia ?aaoeyoe?y aaeuei?aii? neiaioe/ii? ia?aaea/? iae?ii?a
a?iieaiio uo??a aeieaoi?aie eae??aeo eaiae?a // Iae?io?c?ieia?y,
1998.-o.30,?4- noi?.336-340.

2. Ina?aa I.A., Oaaeoeiaa N.A., Aanaeianueeee I.N. Iioaioe?ae- caeaaei?
eaeueoe??a? eaiaee a eoeueoeaiaaieo iae?iiao a?iieaiio uo??a //
Iae?io?c?ieia?y.-1998. -o.30, ?5 -noi?.361-365.

3. Ina?aa I.A. Aieea i?oaae?i?io o aenieeo eiioeaio?aoe?yo ia
aaeuei?aio neiaioe/io ia?aaea/o // Iae?io?c?ieia?y.- 1999 -o.31,
?1-noi?.64-67.

Oace aeiiia?aeae:

1. Isaeva E. V., Vasilyev D. V., Fedulova S. A., Veselovsky N.S. Evoked
and spontaneous excitatory postsynaptic currents in cultured hippocampal
neurons // Neurophysiology. — 1997. -29, 4/5. — p.369

2. Vasilyev D. V., Fedulova S. A., Isaeva E. V., Veselovsky N.S. Effect
of different concentration of the extracellular Ca2+ effect on evoked
inhibitory postsynaptic currents at single synapses of cultured
hippocampal neurons. OOVIII Annual Meeting of Neuroscience Society.
1998. Abstract Book.

Aiioaoe??:

?na?aa I. A. ?ieue iioaioe?ae-ea?iaaieo eaeueoe??aeo eaiae?a a
aaeuei?ai?e neiaioe/i?e ia?aaea/? eoeueoeaiaaieo iae?ii?a a?iieaiio
uo??a.- ?oeiien.

Aeena?oaoe?y ia caeiaoooy a/aiiai nooiaiy eaiaeeaeaoo a?ieia?/ieo iaoe
ca niaoe?aeuei?noth 03.00.13- o?c?ieia?y ethaeeie oa oaa?ei. — ?inoeooo
o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie. Ee?a — 1999.

Aeena?oaoe?y i?enay/aia aeine?aeaeaiith iniiaieo yeaeo?io?ce/ieo oa
oa?iaeieia?/ieo oa?aeoa?enoee aeeeeeaieo aaeuei?aieo iinoneiaioe/ieo
no?oi?a o i?ioean? ?icaeoeo eoeueoo?e iae?ii?a a?iieaiio uo??a ? ?ie?
??ciiiai?oieo iioaioe?ae-ea?iaaieo Na2+ eaiae?a o aaeuei?ai?e
neiaioe/i?e ia?aaea/?. ?acoeueoaoe i?iaaaeaieo aeine?aeaeaiue iieacaee,
ui ?c ca?eueoaiiyi o?eaaeino? eoeueoeaoaaiiy iae?ii?a na?aaeiy
aiie?ooaea aeeeeeaieo aaeuei?aieo iinoneiaioe/ieo no?oi?a oa ?oiy
aiie?ooaeia aaoa?iaaii?noue noaoenoe/ii aeinoia??ii ca?eueooaaeenue,
oiae? ye ?iceeae na?aaeiuei? aiie?ooaee no?oi?a, ui ?a?no?oaaeeny a?ae
iaeeie/ii? ia?e iae?ii?a, ia ci?ithaaany. Iieacaii, ui aaeuei?aia
neiaioe/ia ia?aaea/a a iae?iiao a?iieaiio in vitro aieiaiei /eiii
iiina?aaeeo?oueny aenieiii?iaiaeie Ca2+ eaiaeaie. Ia iniia? /ooeeaino?
aei niaoeeo?/ieo aeieaoi??a anoaiiaeaii, ui L-oei Ca2+ no?oi?a
(aeieoaaany 10 ieI ieoaae?i?io) ia ca’ycaiee c aaeuei?aiith neiaioe/iith
ia?aaea/ath, oiae? ye -CTx-GVIA (N-oei), -Aga-?VA (P -Q-oeie) /ooeea?
eiiiiiaioe, eiiiiiaio /ooeeaee aei aenieeo eiioeaio?aoeue ieoaae?i?io ?
ia/ooeeaee aei oeeo i?aai?/ieo aeieaoi??a eiiiiiaio Ca2+ no?oio aa?ooue
o/anoue a aaeuei?ai?e neiaioe/i?e ia?aaea/? iae?ii?a, ui
aeine?aeaeoaaeeny.

Eeth/ia? neiaa: aaeuei?aia neiaioe/ia ia?aaea/a, iioaioe?ae-ea?iaai?
eaeueoe??a? eaiaee, AAIEA ?aoeaioi?e, a?iieaii.

Enaaaa A. A. ?ieue iioaioeeae-oi?aaeyaiuo eaeueoeeaauo eaiaeia a
oi?iiciie neiaioe/aneie ia?aaea/a eoeueoeae?oaiuo iae?iiia aeiiieaiia
e?un. — ?oeiienue.

Aeena?oaoeey ia nieneaiea o/aiie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe
ii niaoeeaeueiinoe 03.00.13 — oeceieiaey /aeiaaea e aeeaioiuo. —
Einoeooo oeceieiaee ei. A. A.Aiaiiieueoea IAI Oe?aeiu. Eeaa — 1999.

Aeenna?oaoeey iinayuaia enneaaeiaaieth iniiaiuo yeaeo?ioece/aneeo e
oa?iaeieiae/aneeo oa?aeoa?enoee aucaaiiuo oi?iiciuo iinoneiaioe/aneeo
oieia a oiaea ?acaeoey eoeueoo?u iae?iiia aeiiieaiia e?un e ?iee
?acee/iuo iioaioeeae-oi?aaeyaiuo Na2+ eaiaeia a oi?iiciie neiaioe/aneie
ia?aaea/a. Enneaaeiaaiiua a ianoiyuae ?aaioa iinoneiaioe/aneea oiee
aeaiiino?e?iaaee ecaanoiua naienoaa oaeeo oieia, ?aaeno?e?oaiuo a
oi?iiciuo neiainao. Eo iioaioeeae-caaeneiinoue oi?ioi iienuaaeanue
o?aaiaieai Ia?inoa aeey eiiia Nl-, yaeythueieny iniiaiui ia?aiin/eeii
o?ainiaia?aiiiai oiea i?e aeoeaaoeee AAIE-?aoeaioi?ia. aOINO
iieiinoueth aeiee?iaaeenue aeeoeoeeeiii, /oi naeaeaoaeuenoaiaoao i oii,
/oi ?aoeaioi?u iinoneiaioe/aneie iaia?aiu enneaaeiaaiiuo iae?iiia
ioiineeenue e AAIE ?aoeaioi?ai oeia A .

?acoeueoaou i?iaaaeaiiuo enneaaeiaaiee iieacaee, /oi n oaaee/aieai
aeeeoaeueiinoe eoeueoeae?iaaiey iae?iiia n?aaeiyy aiieeooaea aucaaiiuo
oi?iiciuo iinoneiaioe/aneeo oieia e eo aiieeooaeiay aaoa?iaaiiinoue
noaoenoe/anee aeinoiaa?ii oaaee/eaaeenue, oiaaea eae eiyooeoeeaio
aa?eaoeee iaeneiaeueiie aiieeooaeu oieia, ?aaeno?e?oaiuo io aaeeie/iie
ia?u iae?iiia, ia eciaiyeny. Eae oaaee/aiea n?aaeieo aiieeooae oieia,
oae e oaaee/aiea eo ?aca?ina n aic?anoii iae?iiia a eoeueoo?a iiaeii
iauynieoue oaaee/aieai eiee/anoaa neiaioe/aneeo naycae iaaeaeo
ioaeaeueiuie iae?iiaie e oneiaeiaieai no?oeoo?u iae?iiaeueiie naoe a
i?ioeanna ?inoa e aeeooa?aioee?iaee iae?iiia a eoeueoo?a. Oio oaeo, /oi
ioiineoaeueiia n?aaeiaa ioeeiiaiea cia/aiee iaeneiaeueiuo aiieeooae
oieia, ?aaeno?e?oaiuo io eaaeaeie ioaeaeueiie ia?u eeaoie, eae i?e
i?inoie (iieiaeay eoeueoo?a), oae e i?e neiaeiie (ac?ineay eoeueoo?a)
ia?aiie naoe, ia iaiyeinue, iiaeao naeaeaoaeuenoaiaaoue i oii, /oi iii
iaania/eaaaony ia iaiaeii?iaeiinoueth ?ani?ino?aiaiey iioaioeeaea
aeaenoaey ii aeniio a neeo ?acee/iuo eaaaeueiuo naienoa ioaeaeueiuo aai
aaoaae, a, ii anae aeaeeiinoe, eaaioiauie naienoaaie ioaeaeueiuo
neiaioe/aneeo eiioaeoia.

Enoiaey ec iieo/aiiuo aeaiiuo, a iae?iiao aeiiieaiia ia 10-12 aeaiue
eoeueoeae?iaaiey i?enoonoaiaaee ieceiii?iaiaue e aunieiii?iaiaue
eiiiiiaiou eaeueoeeaaiai oiea. Aunieiii?iaiaue eiiiiiaio ii
oa?iaeieiae/aneie /oanoaeoaeueiinoe e i?aaie/aneei aeieaoi?ai Na2+
eaiaeia, aue ?acaeaeai ia ieoaaeeiei-, -CTx-GVIA, -Aga-IVA
-/oanoaeoaeueiua eiiiiiaiou e eiiiiiaio ia /oanoaeoaeueiue e i?eiaiaiiui
aeieaoi?ai. Aeey enneaaeiaaiey aiciiaeiie ?iee ieceiii?iaiaiai
eiiiiiaioa eaeueoeeaaiai oiea a oi?iiciie neiaioe/aneie ia?aaea/a
eniieueciaaeny ianaeaeoeaiue aeieaoi? eaeueoeeaauo eaiaeia Cd2+.
I?eeiaeaiea iaeuo eiioeaio?aoeee yoiai iai?aaie/aneiai aeieaoi?a (10
ieM) aucuaaei neeueiia oiaiueoaiea aiieeooaeu aunieiii?iaiauo
eaeueoeeaauo oieia e aOINO, e ia eiaei nouanoaaiiiai yooaeoa ia
aiieeooaeo ieceiii?iaiaiai eaeueoeeaaiai oiea. Enoiaey ec yoeo aeaiiuo
aue naeaeai auaiae i oii, /oi ieceiii?iaiaua eaeueoeeaaua eaiaeu,
ii-aeaeeiiio, ia o/anoaotho a neiaioe/aneie ia?aaea/a enneaaeiaaiiuo
iaei?iiia. Aeey enneaaeiaaiey o/anoey ?acee/iuo oeiia aunieiii?iaiauo
eaeueoeeaauo eaiaeia a oi?iiciie neiaioe/aneie ia?aaea/a
eniieueciaaeenue naeaeoeaiua eiioeaio?aoeee i?aaie/aneeo eaeueoeeaauo
aeieaoi?ia: 10ieM ieoaaeeieia (aeieaoi? L-oeia Ca2+ eaiaeia), 1ieM
-CTx-GVIA (aeieaoi? N-oeia Ca2+ eaiaeia), 200iM -Aga-IVA (aeieaoi?
P-Q-oeiia Ca2+ eaiaeia). Iieacaii, /oi ieoaaeeiei, yaeythueeny
niaoeeoe/aneei aeieaoi?ii L-oeia Ca2+ eaiaeia a eiioeaio?aoeee 10ieM ia
ieacuaae nouanoaaiiiai yooaeoa ia aiieeooaeo aOINO, oiaaea eae i?e
aiieeeaoeee aieaa aunieeo eiioeaio?aoeee ieoaaeeieia (50, 100 ieM)
aiieeooaea aunieiii?iaiaiai Ca2+ oiea aeiee?iaaeanue ia 17% e 34%,
niioaaonoaaiii. OINO auee /oanoaeoaeueiu e -CTx-GVIA, -Aga-IVA. I?e
niaianoiie aiieeeaoeee aunieeo eiioeaio?aoeee ieoaaeeieia, -CTx-GVIA e
-Aga-IVA 15% aOINO ia aeiee?iaaeinue, /oi naeaeaoaeuenoaoao i oii, /oi
ae?oaea oeiu eaeueoeeaauo oieia ia/oanoaeoaeueiua e aeieaoi?ai L-, N-,
P-Q- oeiia Ca2+ eaiaeia (T-,R-oeiu eee ae?oaea iaeaeaioeoeoee?iaaiiua
oeiu) i?enoonoaotho eioaa?aeueiii Ca2+ oiea, iaania/eaathuai aoiae Na2+
a i?aneiaioe/aneoth oa?ieiaeue e caione iaoaiecia aua?ina iaaeeaoi?a.
Iieo/aiiua aeaiiua iicaieeee naeaeaoue auaiae i oii, /oi L-oei Ca2+
eaiaeia ia naycai n neiaioe/aneie ia?aaea/ae, oiaaea eae -CTx-GVIA
(N-oei)-, -Aga-IVA (P-Q-oei)-/oanoaeoaeueiua eiiiiiaiou, eiiiiiaio
/oanoaeoaeueiue e aunieei eiioeaio?aoeeyi ieoaaeeieia e
ia/oanoaeoaeueiue e yoei i?aaie/aneei aeieaoi?ai eiiiiiaio Na2+ oiea
o/anoaotho a oi?iiciie neiaioe/aneie ia?aaea/a enneaaeiaaiiuo iae?iiia.

Eeth/aaua neiaa: oi?iiciay neiaioe/aneay ia?aaea/a,
iioaioeeae-oi?aaeyaiua eaeueoeeaaua eaiaeu, AAIEA ?aoeaioi?u, aeiiieaii.

Isaeva E. V. The participation of voltage-activated Ca2+ channels in
inhibitory synaptic transmission at the culture of rat hippocampal
neurons. — Manuscript.

Thesis for PhD degree by specialty 03.00.13. — human and animal
physiology. — Bogomoletz institute of Physiology NASc of Ukraine. Kiev —
1999.

The dissertation is devoted to investigation of electrophysical and
pharmacological properties evoked inhibitory postsynaptic currents of
developing rat hippocampal neurons in vitro and the participation of
different voltage-activated Ca2+ channels in inhibitory synaptic
transmission. The obtained results indicated that enlargement of
cultivating term caused an increase of the average amplitude of evoked
inhibitory postsynaptic currents and their amplitudes variations,
whereas deviation of the average current amplitudes didn`t change. It
was shown, that inhibitory transmission in hippocampal neurons in vitro
was mediated mainly by HVA Ca2+ currents. On the base of diffrent
sensitivity to specific Ca2+ channel blockers it was indicated that
L-type Na2+ current (blocked by 10I nifedipine) not involved in
sinaptic transmission, whereas -CTx-GVIA (N-type) and -Aga-IVA
(P-Q-type) -sensitive components, sensitive to high concentrations
nifedipine component and insensitive to this organic blockers component
of Ca2+ current participated in triggering inhibitory neurotransmitter
release in hippocampal neurons.

Key words: inhibitory synaptic transmission, voltage-activated Ca2+
channels, GABAA receptors, hippocamp.

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