IAOe?IIAEUeIA AEAAeAI?ss IAOE OE?A?IE

?INOEOOO O?C?IEIA?? ?i. I.I.AIAIIIEUeOess

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A?EUAIEI IEAEN?E AAAeEIIAE*

OAeE 611.127:612.179.1, 577.352.5.

Aeine?aeaeaiiy eae??aeo eaiae?a oa ?o ?ie? a ea?ae?ii?ioeeoao,
aeeoa?aioe?eiaaieo c aia??iiaeueieo noiaao?iaeo ee?oei ieo?

03.00.02 — a?io?ceea

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

eaiaeeaeaoa a?ieia?/ieo iaoe

Ee?a — 1998 ?. 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, i?io., aeaaeai?e IAIO
Einothe Ieaoii A?eai?iae/

?inoeooo o?c?ieia?? ?i.I.I.Aiaiiieueoey IAI Oe?a?ie, aee?aeoi?

Io?oe?ei? iiiiaioe:

Aeieoi? a?ieia?/ieo iaoe, i?ioani? eaoaae?e a?io?ceee Iaoe?iiaeueiiai
oi?aa?neoaoo ?i. Oa?ana Oaa/aiea Ceia Aaeaioei Eaii?aeiae/

Eaiaeeaeao a?ieia?/ieo iaoe, a/aiee nae?aoa? I?aeia?iaeiiai oeaio?o
iieaeoey?ii? o?c?ieia?? Oaaeoeiaa Na?oeaia Aiaoie??aia

I?ia?aeia onoaiiaa: ?inoeooo iieaeoey?ii? a?ieia?? oa aaiaoeee, i. Ee?a

Caoeno a?aeaoaeaoueny “__29__”__a?oaeiy_____1998 ?. i __11-00_ aiaeei?
ia can?aeaii? niaoe?ae?ciaaii? a/aii? ?aaee Ae-01.13.01 i?e ?inoeooo?
?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
?i.I.I.Aiaiiieueoey, i. Ee?a, aoe. Aiaiiieueoey, 4.

Aaoi?aoa?ao ?ic?neaiee “_26_”___eenoiiaaea____1998 ?.

A/aiee nae?aoa?

niaoe?ae?ciaaii? a/aii? ?aaee,

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

ANOOI

Aeooaeuei?noue i?iaeaie

I?ae /an i?aiaoaeueiiai ia??iaeo ?icaeoeo o?aaaoieo oaa?ei oi?iothoueny
??ci? i?aaie ? ii/eiathoue aeyaeyoeny i?eoaiaii? ?i ooieoe??. Na?oea ?
ia?oei i?aaiii aia??iio, ui aeinyaa? ooieoe?iiaeueiiai noaio. Oiio
aia??iiaeueiee ?icaeoie oa ?aii? ?icaeiaiiy aeaeo?io?c?ieia?/ieo oa
iia’ycaieo c ieie ooieoe?e i?eaa?oathoue aei naaa cia/io oaaao. Aea
o?c?ieia?/ia aeine?aeaeaiiy ooieoe?e na?oey, a oiio /ene? aeaeo?e/ieo
aeanoeainoae, ui iaoiiaeththoue ?aiiey?ecaoe?th iioaioe?ae?a ae?? a
ee?oeiao na?oey aia??iio, iaiaaeoaaeinue neeaaei?noth canoinoaaiiy
noaiaea?oieo aeaeo?io?c?ieia?/ieo iaoiae?a. Aea/aiith aeni?an?? ?iiieo
eaiae?a i?ae /an ?aiiueiai ia??iaeo ?icaeoeo aia??iio nnaaoe?a
ia?aoeiaeaea? iaeaiueeee ?ici?? aia??iiaeueiiai na?oey oa a?aenooi?noue
noaa?eueieo ee?oeiieo e?i?e aeey iiaeaethaaiiy i?aiaoaeueieo noaae?e
ea?ae?ii?iaaiaco. Iia? iiaeeeaino? aeey aea/aiiy ?aii?o noaae?e
ea?ae?ii?iaaiaco aoee iauiaeaaii i?iaeaiiino?iaai? c aeei?enoaiiyi
ea?ae?ii?ioeeo?a, aeeoa?aioe?eiaaieo in vitro c aia??iiaeueieo
noiaao?iaeo ee?oei ieo?.

Iaoa aeine?aeaeaiiy

Aea/eoe ca’ycai? c a?eii ci?ie aeni?an?? eae??aeo eaiae?a, ui eaaeaoue a
iniia? ?aiiey?ecaoe?? iioaioe?aeo ae?? na?oeaaeo ee?oei, oa ?ieue
no?oi?a /a?ac oe? eaiaee a noaa?e?caoe?? ?eoi?/ii? aeoeaiino? ?aii?o
ea?ae?ii?ioeeo?a.

Caaaeaiiy aeine?aeaeaiiy

Aecia/eoe oeie aeo?aeieo eae??aeo no?oi?a a ea?ae?ii?ioeeoao,
aeeoa?aioe?eiaaieo in vitro c aia??iiaeueieo noiaao?iaeo ee?oei.

C’ynoaaoe caeaaei?noue aeni?an?? eae??aeo eaiae?a aeo?aeiiai aei?yieaiiy
a?ae /ano aeeoa?aioe?thaaiiy ea?ae?ii?ioeeo?a in vitro.

Aecia/eoe ?ieue AOO-caeaaeieo eae??aeo eaiae?a aeo?aeiiai aei?yieaiiy
?aii?o ea?ae?ii?ioeeo?a a ?aaoeyoe?? oa noaa?e?caoe?? aeaeo?e/ii?
aeoeaiino? ee?oei.

Aea/eoe aieea ci?ie iicaee?oeiii? eiioeaio?aoe?? ?ii?a eae?th ia
oaeaeeee o?aic??ioiee eae??aee no?oi.

Iaoeiaa iiaecia ?iaioe

Iieacai? ci?ie aeni?an?? ??cieo oei?a eae??aeo eaiae?a aeo?aeiiai
aei?yieaiiy i?ae /an ?aiiueiai ea?ae?ii?iaaiaco i?ioeeo?a,
aeeoa?aioe?eiaaieo c aia??iiaeueieo noiaao?iaeo ee?oei ieo?. Iieacaia
iniaeeai aaaeeeaa ?ieue eaiae?a oaeaeeiai eae??aiai (Ito) no?oio o
oi?ioaaii? oa i?aeo?eioe? noaa?eueii? ?eoi?/ii? aeoeaiino?
ea?ae?ii?ioeeo?a ia iaea?eueo ?aiiueiio no?ieia? aeeoa?aioe?eiaee — a?ae
iaei??? aei /ioe?ueio ae?a i?ney iiyae niiioaiieo, ?eoi?/ieo nei?i/aiue
ee?oei.

Aeyaeaii, ui ia a?aei?io a?ae ?ioeo oei?a eae??aeo eaiae?a, AOO-caeaaei?
eaiaee aeni?anothoueny i?aeoe/ii a on?o ea?ae?ii?ioeeoao iacaeaaeii a?ae
no?ieo ae?oa?aioe?thaaiiy, a aonoeia no?oi?a e??cue oe? eaiaee i?aeoe/ii
ia ci?ith?oueny c a?eii ee?oei. Iieacaia ?ieue eaiae?a, ui aeoeaothoueny
AOO, a ci?iao aeaeo?e/ii? aeoeaiino? ea?ae?ii?ioeeo?a, ui aeieeathoue
i?e ci?iao aia?aaoe/iiai iaoaaie?cio ee?oeie.

Aecia/ai? iaoai?cie aieeao iicaee?oeiii? eiioeaio?aoe?? E+ ia
ooieoe?iioaaiiy eae??aeo eaiae?a o?aic??ioiiai no?oio, ui iaoiiaeai?
?ii-eiioi?iaoe?eiith aca?iiae??th a?eea, ui oi?io? eaiae, oa ?ii?a, ui
i?ioiaeyoue e??cue iueiai.

Oai?aoe/ia oa i?aeoe/ia cia/aiiy ?iaioe

Iienai? yaeua iiaeooue iaoe aaciina?aaei? a?aeiioaiiy aei i?ioeano
noaa?e?caoe?? nei?i/oaaeueii? aeoeaiino? i?iea?ae?aeueieo ee?oei a
i?ioean? i?aiaoaeueiiai ?icaeoeo oa aei i?ciaiiy i?ioean?a, ui eaaeaoue
a iniia? iioiaaiaoe/iiai noaaeaiiy ?iiieo eaiae?a iaia?ai
ea?ae?ii?ioeeo?a, ui ia? ye oai?aoe/ia, oae ? i?aeoe/ia cia/aiiy aeey
?ic?iaee iiaeo aeae?a e?ea?nueeeo i?aia?ao?a.

Iniaenoee aianie

An? aenia?eiaioe, i?eaaaeai? a oe?e ?iaio?, aoee aeeiiai? aaoi?ii
iniaenoi. A ?ic?iaoe? eiioeaioe?e ?iaioe oaeiae i?eeiaee aeoeaio o/anoue
?io? ni?aaaoi?e ioae?eaoe?e.

Ai?iaaoe?y ?iaioe

Iniiai? iieiaeaiiy ?iaioe aeiiia?aeaeenue ? iaaiai?thaaeenue ia iaoeiaeo
nai?ia?ao ?inoeoooo o?c?ieia?? ?i. I.I.Aiaiiieueoey IAI Oe?a?ie (1995),
?inoeoooo iae?io?c?ieia?? oi?aa?neoaoo i. Eaeuei (I?ia//eia, 1996), ia
ia?oiio nai?ia?? I?iaoeueei-Oe?a?inueei? aeine?aeieoeueei? a?oie (Ee?a,
1996), ia ui??/iiio c’?cae? o?c?ieia?a I?ia//eie (1997). Ca iaoa??aeaie
aeena?oaoe?? iioae?eiaaii 3 noaoo? o i?aeia?iaeieo iaoeiaeo aeo?iaeao.

Ianya oa no?oeoo?a aeena?oaoe??

Aeena?oaoe?y neeaaea?oueny c anooio, iaeyaeo e?oa?aoo?e, iieno iaoiae?a
aeine?aeaeaiiy, ?acoeueoao?a aeine?aeaeaiiy, aeniiae?a oa nieneo
e?oa?aoo?e c 141 iaeiaioaaiue. ?iaioa aeeeaaeaia ia 104 noi??ieao,
?ethno?iaaia 20 iaethieaie.

IAOIAeEEA AeINEIAeAEAIUe

Ia’?eo aeine?aeaeaiiy. A?eueo?noue aenia?eiaio?a aoei i?iaaaeaii ia
ea?ae?ii?ioeeoao, aeeoa?aioe?eiaaieo a oiiaao eoeueoo?e c aia??iiaeueieo
noiaao?iaeo ee?oei ieo?. Aeey oeueiai e?aieeie noniaic?? noiaao?iaeo
ee?oei e?i?? D3 (400 ee?oei o 20 iee ?ic/eio) eoeueoeaoaaeeny aea? aeiae
ia e?eoa/eao /aoie Iao??. Ca oeae /an oi?ioaaeeny noa?e/i?, oae caai?
aia??iiaeuei? o?eueoey. Ianooii? 5 ae?a aiie ia?aiineeeny o aaeee? /aoee
Iao?? ? eoeueoeaoaaeeny o noniaic??. Iio?i naieaeaii? aia??iiaeuei?
o?eueoey ?iciiae?eyeeny o 24-eoieia? ieaoe — iaeia o?eueoea ia eoieo.
Ianooiiiai aeiy iiaeia aoei aa/eoe eeanoa?e ea?ae?ii?ioeeo?a, ui
niiioaiii nei?i/oaaeeny. Ca aeiiiiiaith oa?iaioaoeaii? ia?iaee ie
io?eioaaee iiiaeeiie? ea?ae?ii?ioeeoe, ui niiioaiii oa ?eoi?/ii
nei?i/oaaeeny. Ia 2-4 aeiao i?ney iiyae ia?oeo ee?oei, ui
nei?i/oaaeenue, ie io?eioaaee i?ioeeoe “?aiiueiai” no?ieo
aeeoa?aioe?thaaiiy, a ia 9-11 aeiao — ee?oeie “i?ciueiai” no?ieo
aeeoa?aioe?thaaiiy.

Ee?oeie e?i?? GH3 eoeueoeaoaaeenue a iiiioa?? a na?aaeiaeu? RPMI 1640 c
aeiaeaaaiiyi 10 % ae/i? ne?iaaoee a aoiinoa??, ui i?noeea 5% NI2 i?e 37i
N.

?a?no?aoe?y oa ia?iaea ?acoeueoao?a. O?ainiaia?aii? no?oie
aei??thaaeenue o ?aaeei? o?enaoe?? iaia?aiiiai iioaioe?aeo — iaoiaeeea
patch-clamp a eiio?ao?aoe?? “oe?ea ee?oeia” (Hamil et al. 1981) oa
iiaeeo?eiaai?e eiio?ao?aoe?? — “whole-cell perforated patch” ?c
aeei?enoaiiyi aioea?ioeea aioioe??oeeio A (Rae et al., 1991). Neeyi?
i?e?ii?iaoee ae?iaeyeenue ?c eaaeiieaaeeo eai?ey??a ae?aiao?ii 1,8 ii.
Aeey aeae?eaiiy eae??aeo no?oi?a aeei?enoiaoaaany aaciao???aee ?ic/ei,
yeee i?noea ( o iI): KCl 5, MgCl2 1, CaCl2 1.8, Choline-Chloride 140,
HEPES 10, CdCl2 0.1, pH 7.45 (KOH); aioo??oi?e ?ic/ei iaa oaeee neeaae (
o iI): KCl — 150, EGTA 10, CaCl2 1, MgCl2 1, HEPES 10, pH 7.4 (EOI); o
aeiaaeeo ia?oi?iaaiiai aa??aioo patch-clamp aeei?enoiaoaaany o?ioe ?ioee
?ic/ei, a naia (o iI): KCl 55, MgCl2 7, HEPES 10, K2SO4 70, pH 7.45.

?a?no?aoe?y no?oi?a i?iaiaeeeanue i?e aeei?enoaii? aiaeiaiaiai
i?aeneethaa/a Axopatch 200 A. On? io?eiai? aeai? caienoaaeenue ia
eiii’thoa? oa ia?iaeyeenue ca aeiiiiiaith niaoe?aeueieo i?ia?ai.
Ia/enethaaiiy ia?aiao??a no?oi?a i?iaiaeeeinue i?ia?aiaie Datasel oa ISO
2, a ianooiia iaoaiaoe/ia ia?iaea aeaieo oa iiaoaeoaa iaethie?a — Sigma
Plot.

?a?no?aoe?y no?oi?a ia ea?ae?ii?ioeeoao i?iaiaeeeanue i?e oaiia?aoo??
320N, ia ee?oeiao e?i?? GH3 — i?e e?iiaoi?e oaiia?aoo??. No?oi aeoieo
eiiiainoaaany aiaeiaiai oa c aeei?enoaiiyi i?ioeaaeo?e ?/4 oa
eiio?iethaaany ai?iaeiaae anueiai aenia?eiaioo. Aiie?ooaea no?oio
iaea?aeoaaeanue ye ??cieoey i?ae i?eiaei cia/aiiyi no?oio oa ioeueiaith
e?i??th. Io?eiai? ?acoeueoaoe i?aaenoaaeai? o iaeeieoeyo ( n.n.i.
(na?aaeiy noaoenoe/ia iiieeea).

?ACOEUeOAOE AeINE???IAeAEAIUe

Aeey aea/aiiy ci?i aeni?an?? E+ eaiae?a i?ae /an aeeoa?aioe?thaaiiy oa
?o ?ie? a ea?ae?ii?ioeeoao ie aeei?enoiaoaaee aea? a?oie ee?oei — ?aii?
ee?oeie (7+2 — 7+4 ae?a niaoe?aeueiiai i?ioieieo eoeueoeaoaaiiy) oa
i?ci? ea?ae?ii?ioeeoe (7+9 — 7+14 ae?a eoeueoeaoaaiiy).

?icae?eaiiy eae??aiai no?oio ia eiiiiiaioe

Aeei?enoiaoth/e 4-ai?iii???ae?i ie aeae?eyee o?e ??ci? eiiiiiaioe
eae??aiai no?oio , ui iaee ??cio e?iaoeeo oa ??cio /ooeea?noue aei 4-AI.
E+ no?oi aeeeeeaany aeaiiey?ecaoe??th a?ae -40 iA aei +80 iA a?ae
i?aeo?eioaaiiai iioaioe?aeo -80 iA. An? eiiiiiaioe iaee oaeaeeo
aeoeaaoe?th, aea ??cio e?iaoeeo ?iaeoeaaoe??. Oaeaeea eiiiiiaioa no?oio
(Ito ) aoea /ooeeaa aei ciai?oiueiai i?eeeaaeaiiy 4-AI (EAe= 1.7 iI),
eiiiiiaioa c iia?eueiith ?iaeoeaaoe??th (Islow) aoea iaae/ooeeaith aei
4-AI (EAe= 29 ieI) oa eiiiiiaioa, ui ia?iaeoeao?oueny (Isus), aoea
ia/ooeeaa aei 4-AI (?en.1).

?iciiae?e oa ci?ia aonoeie ??cieo eiiiiiaio E+ no?oio

Ne?ae a?aei?oeoe, ui aianie ??cieo eiiiiiaio aei eae??aiai no?oio aoa
??ciee o ??cieo ee?oei ? caeaaeaa a?ae /ano aeeoa?aioe?thaaiiy
ea?ae?ii?ioeeo?a. Aoee aeyaeai? aea? iiioeyoe?? ee?oei, ui a?ae??ciyeeny
??cieie i?iii?oe?yie aeni?an?? ??cieo oei?a E+ eaiae?a. A 75%
ea?ae?ii?ioeeo?a ?aiiuei? noaae?? aeeoa?aioe?thaaiiy (n=72) aoee
aeyaeai? o?eueee aea? eiiiiiaioe eae??aiai no?oio aeo?aeiiai
aei?yieaiiy: eiiiiiaioa ?c oaeaeeith ?iaeoeaaoe??th (Ito ) oa
eiiiiiaioa, ui ia?iaeoeaoaaeanue (Isus). A ?aoo? 25% ee?oei
niinoa??aaeanue ? o?aoy eiiiiiaioa c iia?eueiith ?iaeoeaaoe??th (Islow).
A ea?ae?ii?ioeeoao i?ciuei? noaae?? aeeoa?aioe?thaaiiy oeae ?iciiae?e
aoa o?ioe ?ioee: 69% oa 31% a?aeiia?aeii. A ae?oa?e iiioeyoe?? ee?oei ie
niinoa??aaee iayai?noue an?o o?ueio eiiiiiaio eae??aiai no?oio (?en.2).

?en.1 ?icae?eaiiy E+ no?oio ia eiiiiiaioe ca aeiiiiiaith 4-AI. IK,
aeeeeeai? nooi?i/aoith aeaiiey??caoe??th iaia?aie a?ae 0 iA aei 80 iA c
e?ieii 20 iA a?ae i?aeo?eioaaiiai iioaioe?aeo -80 iA: 1 — a eiio?ie?; 2
? 3 — i?ney i?eeeaaeaiiy 0.3 iI oa 10 iI 4-AI, a?aeiia?aeii; Ito oa
Islow, io?eiai? ae?aooaaiiyi ?c caien?a no?oi?a (3 c 2 oa 2 c 1,
a?aeiia?aeii). ?en.2 Ci?ie ?iciiae?eo aonoeie eiiiiiaio E+ no?oio c
a?eii ea?ae?ii?ioeeo?a. 1 — eiiiiiaioa Ito, 2 — Isus, 3 — Islow.
Eae??aee no?oi aeeeeeaany aeaiiey?ecaoe??th iaia?aie a?ae -80 iA aei 40
iA; n — /enei ee?oei.

?ieue ??cieo eiiiiiaio E+ no?oio a noaa?e?caoe?? aeaeo?e/ii? aeoeaiino?

Ie ia?aa??eee ae?th 4-AI ia /anoioo aaia?aoe?? oa oi?io iioaioe?ae?a
ae?? ea?ae?ii?ioeeo?a, ui niiioaiii nei?i/oaaeeny. A i?ci?o ee?oeiao
i?eeeaaeaiiy 4-AI a iicaee?oeiiee ?ic/ei ia ci?ithaaei /anoioo
aaia?aoe?? iioaioe?ae?a ae??, aai oe? ci?ie aoee iacia/ieie (1.1(0.03,
n=9). A oie aea /an aeaeo?e/ia aeoeai?noue ea?ae?ii?ioeeo?a a ?aii?e
noaae?? aeeoa?aioe?thaaiiy aoea /ooeeaa aei i?eeeaaeaiiy 4-AI. Oae,
iai?eeeaae, i?eeeaaeaiiy 10 iI 4-AI i?eaiaeeei aei ca?eueoaiiy /anoioe
aaia?aoe?? iioaioe?ae?a ae?? i?eaeecii aaea?/? (1.83(0.088, n=5) ? oeae
aoaeo aoa cai?ioi?i. Aeiaeaaaiiy 10 iI 4-AI a iicaee?oeiiee ?ic/ei ia
aieeaaei ia i?ci? ee?oeie, aea i?eaiaeeei aei ca?eueoaiiy o?eaaeino?
(aei??yiiai ia ??ai? ioeueiaiai iioaioe?aeo) iioaioe?ae?a ae?? ?ai?o
ee?oei (11(0.8 %, n=5).

A ee?oeiao, ui iaee aeineoue aaeeeo Islow eiiiiiaioo, i?eeeaaeaiiy 100
ieI 4-AI ia i?ecaiaeeei aei ci?ie /anoioe aaia?aoe?? iioaioe?ae?a ae??.
Ie c?iaeee aeniiaie, ui oey eiiiiiaioa ia a?ae?a?a? aaeeei? ?ie? a
noaa?e?caoe?? aeaeo?e/ii? aeoeaiino? ea?ae?ii?ioeeo?a.

Aeiaeaaaiiy a iicaee?oeiiee ?ic/ei iaaaeeei? eiioeaio?aoe?? Aa2+ (a?ae
50 aei 100 ieI), ye eeane/iiai aeieaoi?o eaiae?a IK1, oaae ia aieeaaei
ia /anoioo aaia?aoe?? iioaioe?ae?a ae?? ee?oei. Oi ae ie ae?eoee
aeniiaeo, ui iaea?eueo aaaeeeaith eiiiiiaioith eae??aiai no?oio, ui
a?aeiia?aea? ca noaa?e?caoe?th aeaeo?e/ii? aeoeaiino?, a
ea?ae?ii?ioeeoao ?aiiuei? noaae?? aeeoa?aioe?thaaiiy ? eiiiiiaioa Ito. A
i?ci?o ee?oeiao aaeeeo ?ieue a i?aeo?eiaii? /anoioe aaia?aoe??
iioaioe?ae?a ae?? ii/eia? a?ae?a?aaaoe ia/ooeeaa aei 4-AI Isus
eiiiiiaioa eae??aiai no?oio. Noaea /ano aeoiaeo c ?iaeoeaaoe?? Ito
aei??aith? 2.4 nae. Aacoth/enue ia e?iaoe/ieo oa oa?iaeieia?/ieo
aeanoeainoyo oe??? eiiiiiaioe eae??aiai no?oio, ie ae?eoee aeniiaeo, ui
eiaeoth/ei aaiii eaiae?a Ito ? Ev1.4.

AOO-caeaaei? eae??a? eaiaee

Iaaio ?ieue a aaia?aoe?? caoaeaeaiiy oa noaa?e?caoe?? aeaeo?e/ii?
aeoeaiino? ee?oei i?iea?aeo a?ae?a?athoue ? ?io? eae??a? eaiaee,
iai?eeeaae eaiaee Ik1, IAch oa IK,ATO. A i?ioeeaaei?noue eaiaeai Ik1 oa
IAch, ie ia niinoa??aaee aaeeei? ??cieoe? a aonoei? no?oi?a IK,ATO i?ae
?aii?ie oa i?ci?ie ea?ae?ii?ioeeoaie.

A aeayeeo iiiaeeiieeo ea?ae?ii?ioeeoao ie niinoa??aaee aeieeiaiiy
ia?a?eaaiiy aaia?aoe?? iioaioe?ae?a ae??. Oaea aeaeo?e/ia aeoeai?noue
oa?aeoa?ecoaaeany ia??iaeaie (22.6 nae) aaia?aoe?? iioaioe?ae?a ae??,
i?ae yeeie niinoa??aaeeny ia??iaee a?aenooiino? aeaeo?e/ii? aeoeaiino?
(21.1 nae). I?ae /an ia??iaeo aaia?aoe?? IAe ?icaeaaeanue iino?eia
a?ia?iiey?ecaoe?y iaia?aie, iioe?aiiy ?icaeoeo IAe oa niaae /anoioe
iioaioe?ae?a ae??. A ia??iaee a?aenooiino? IAe aeieeaea iino?eia
aeaiiey?ecaoe?y ? i?ney aeinyaiaiiy e?eoe/iiai ??aiy niiioaii? IAe
aeieeaee ciiao (?en.3). ?icaeiaiiy a?ia?iiey?ecaoe?? iaia?aie
ea?ae?ii?ioeeo?a i?ae /an aeoeaiiai ia??iaeo i?eionea? o/anoue a oeueiio
i?ioean? eae??aeo no?oi?a. Aeiaeaaaiiy a eaia?o oain?aa?a?io (aeieaoi?o
na?eiieaciaoe/ii? Ca2+-ATOac), ui i?eaiaeeei aei i?aeaeuaiiy ??aiy
a?eueiiai eaeueoe?th a ee?oei?, ia ci?ithaaei oa?aeoa? aaia?aoe?? IAe
(?en 3). Aei oiai ae a aenia?eiaioao c o?enaoe??th iioaioe?aeo ie i?eiee
ia aa/eee Ca2+-aeoeaiaai? eae??a? no?oie. Ioaea, o/anoue IK,Ca a
aeieeiaii? ia/eiaiai oeio aeaeo?e/ii? aeoeaiino? aeeeeea? noii?ae.

?en.3 Aieea TG ia ia/eiaee oei aeaeo?e/ii? aeoeaiino? ea?ae?ii?ioeeo?a.

Cieco, aeiaeaaaiiy a ?ic/ei oain?aa?a?io (aeieaoi?o na?eiieaciaoe/ii?
Ca2+-ATOac) ia ci?ith? oa?aeoa? aaia?aoe?? iioaioe?ae?a ae??.

Aai??, /anoioa aaia?aoe?? iioaioe?ae?a ae?? a Aoe, iiiaio i?eeeaaeaiiy
TG aeacaiee no??eeith.

?en.4 Caeaaei?noue e?iaoe/ieo ia?aiao??a Ito a?ae ??aiiaaaeiiai
eae??aiai iioaioe?aeo.

E?ai?o/, caeaaei?noue noaei? /ano aeoeaaoe?? Ito a?ae ??aiiaaaeiiai E+
iioaioe?aeo, i?aai?o/ — ia?aiao?o noaoe?iia?ii? aeoeaaoe?? Ito.
I?eaaaeaii ii 3 e?ea?, io?eiaii? aeey ??cieo eiioeaio?aoe?e
iicaee?oeiiiai eae?th — 10, 20 oa 30 iI. Ii in? aanoeen eae??aee
??aiiaaaeiee iioaioe?ae (V-VK).

Oaea ia/eiaa aeoeai?noue ??aeei cono??/aeany ia ?cieueiaaieo
ea?ae?ii?ioeeoao, oi ae i?e?iaeo oa iaoai?cie aeieeiaiiy oaeiai oeio
aeaeo?e/ii? aeoeaiino? ie aea/aee aeei?enoiaoth/e iaoiae aeey o?eaaei?
?a?no?aoe?? — iicaee?oeiia a?aeaaaeaiiy iioaioe?ae?a a?ae iaeanoae
aia??iiaeueiiai o?eueoey, ui nei?i/oaaeenue. Oaeo oeiiao ia/eiaa
aeoeai?noue iiaeia aoei aeeeeeaoe aeaeaeaiiyi iniiaieo “aia?aaoe/ieo”
eiiiiiaio?a eoeueoo?aeueiiai ?ic/eio, aai aeiaeaaaiiyi a ?ic/ei
eiiiiiaio?a, ye? i?aeaeuothoue /anoioo aaia?aoe?? iioaioe?ae?a ae??,
oaeeo, ye Bay K 8644 (aaii?noa L-oeio Ca2+ eaiae?a). I?eeeaaeaiiy
aeieaoi?o IK,ATO ae?aaieeai?aeo (1 iei) i?eaiaeeei aei iiaiiai
i?eai?/aiiy ia/eiai? aeoeaiino?. Ie ae?eoee aeniiaeo, ui IK,ATO ? ?
a?ia?iiey?ecoth/ei no?oiii, ui iaoiiaeth? aeieeiaiiy ia/eiaiai oeio
aeaeo?e/ii? aeoeaiino? ea?ae?ii?ioeeo?a.

Aieea iicaee?oeiii? eiioeaio?aoe?? E+ ia oaeaeeee eae??aee no?oi

I?aeoe/ii an? ea?ae?ii?ioeeoe iaee Ito no?oi. Aea aea/aiith oe???
eiiiiiaioe no?oio ia i?iea?ae?aeueieo ee?oeiao ia?aoeiaeaea? iayai?noue
aaeeei? e?eueeino? oei?a no?oi?a a ee?oeiao oa i?aeoe/ii? iaiiaeeeaino?
aeae?eaiiy Ito eiiiiiaioe a /enoiio aeae?. Oiio aeey iiaeaeueoiai
aea/aiiy aeanoeainoae Ito, ie aeei?enoiaoaaee ee?oeie e?i?? GH3, ye?
aeni?anothoue aiaeia ea?ae?aeueiiai Ito — IA, o?aic??ioiee eae??aee
no?oi (Ev1.4).

E+ no?oi, ui oaeaeei ?iaeoeao?oueny, aeeeeeaany aeaiiey?ecaoe??th aei
-40 iA ? aeua a?ae i?aeo?eioiiai iioaioe?aeo -80 iA. ?a?no?aoe?y
i?iaiaeeeanue i?e oanooth/eo iioaioe?aeao a?ae 0 iA aei +80 iA c e?ieii
20 iA. Ii io?eiaiei ?a?no?aoe?yi no?oi?a aoee ?ic?aoiaai? noae? /ano
aeoeaaoe?? IK (tn) oa cia/aiiy ia?aiao?o noaoe?iia?ii? aeoeaaoe?? (n()
aeey ??cieo eiioeaio?aoe?e E+ a iicaee?oeiiiio ?ic/ei?. Ca?aeii
eeane/ii? iiaeae? Oiaeaee?ia-Oaene? tn oa n( ? ooieoe?yie iaia?aiiiai
iioaioe?aeo ? ia caeaaeaoue a?ae ?iiieo

?en.5 Eiioi?iaoe?eiee iioaioe?ae ?iiiiai eaiaeo c aeaiia i?i?ioiaie.

Eiioi?iaoe?eiee iioaioe?ae aecia/a? e?iaoeeo ooieoe?iioaaiiy ?iiiiai
eaiaeo: eiia??i?noue ?aae?caoe?? noaio, /an aeeooy oa /anoioa ia?aoiae?a
i?ae noaiaie aecia/athoueny cia/aiiyi iioaioe?aeo a oi/eao aeno?aioi?a —
U(x1), U(x2) oa U(x3).

?en.6 Caeaaeiino? oaeaeeinoae ia?aoiae?a ( oa ( a?ae iicaee?oeiii?
eiioeaio?aoe?? ?ii?a eae?th.

Caeaaeiino? ( oa ( a?ae ciai?oiuei? eiioeaio?aoe?? E+ iaaeai? aeey
o?ueio oanooth/eo iioaioe?ae?a: 0, 20 oa 40 iA (aeacai? ia a?ao?eao).
eiioeaio?aoe?e. Aea ie niinoa??aaee cnoa caeaaeiino? tn a?ae cia/aiiy
iaia?aiiiai iioaioe?aeo aiaeii/an ?c ci?iith iioaioe?aeo ?aaa?n??
no?oio. Oeae cnoa iaa iaiiiioiiiee oa?aeoa?. I?e ca?eueoaii?
iicaee?oeiii? [K+] a?ae 10 aei 20 iI caeaaei?noue cnoaaeanue a iai?yieo
a?eueo iecueeeo iioaioe?ae?a, aea aeey eiioeaio?aoe?e caaa?eueoee 20 iI
oey caeaaei?noue cnoaaeanue a iai?yieo a?eueo aenieeo iioaioe?ae?a.
Iiae?aiee aoaeo ie niinoa??aaee ? aeey caeaaeiinoae tn a?ae iaia?aiiiai
iioaioe?aeo ( (?en.4). Caeaaei?noue tn oa n( a?ae iicaee?oeiii? [K+]
iaee aeno?aioie i?e [K+]cia aeecueei 20 iI (?en.4).

Iien ?iaioe ?iiiiai eaiaeo c o?aooaaiiyi ?ii-eiioi?iaoe?eii? aca?iiae??

Iiaeaeue Oiaeaee?ia-Oaene? i?eionea?, ui ??ciiiai?oi? ai?ioi? iaoai?cie
a?aeiia?aeathoue ca a?aee?eaaiiy-cae?eaaiiy eaiaeo oa aecia/athoue
e?iaoeeo ?iiieo eaiae?a. Ai?ioa iiaeooue ciaoiaeeoeny a aeaio iiceoe?yo:
a?aee?eo?e oa cae?eo?e (?en.5). Aea aiie iiaeooue ciaoiaeeoeny a aoaeue
yeiio noai?, a?aeiia?aeii aei iaaiiai cia/aiiy ocaaaeueiaii?
eiioi?iaoe?eii? ci?iii? o. Oey ci?iia iiaea iienoaaoe aoaeoeaiee
ae?aiao? eaiaeo, iieiaeaiiy ca?yaeaeaii? a?oie eaiaeo, yeiai-iaaoaeue
eooiaiai aai iieaeoey?iiai ?ici??o oa ?ioa. Eiaeai noai
oa?aeoa?eco?oueny aia?a??th, ui ? ooieoe??th o — eiioi?iaoe?eiiai
iioaioe?aeo (U(x)). Eiai i?i?ioie aecia/athoue no?ee? noaie: o1
a?aeiia?aea? a?aee?eoiio noaio, o3 — cae?eoiio noaio, a o2 a?aeiia?aea?
iiceoe?? iioaioe?eiiai iaeneioio, ui aecia/a? aia?a?th, yea iaiao?aeia
aeey ia?aoiaeo ?c iaeiiai i?i?ioio a ?ioee. Aoaeoeaiee iioaioe?ae U(x)
iiai?noth aecia/a? e?iaoeeo ia?aoiae?a ? ia? oa?ii-aeoeaiaaio i?e?iaeo.
Oaeaeeino? ia?aoiae?a ( oa ( aecia/athoueny oaeeie ??aiyiiyie:

((ao?((((o3(((((2()/eO(, ((ao?((((o1(((((2()/eO( (1)

aea e — eiinoaioa Aieueoeiaia, O — aaniethoia oaiia?aoo?a.

Aeey iieno ?ii-eiioi?iaoe?eii? aca?iiae?? (?EA) oa ?? aieeao ia
ooieoe?iioaaiiy ?iiiiai eaiaeo ?ic?a’?ii U(x) ia aea? neeaaeia?:
U(x)=H(x)+V(x), aea I(o) — cia/aiiy aia?a?? ai?ioii? a?oie eaiaeo a ?ac?
a?aenooiino? ?iia a eaiae?. Aiia caeaaeeoue a?ae iaia?aiiiai
iioaioe?aeo, aea ia a?ae eiioeaio?aoe?? ?ii?a. V(x) — oea aia?a?y ?EA,
ui aeeth/a? canaeai?noue eaiaeo ?iiaie N ? caeaaeeoue ye a?ae
iaia?aiiiai iioaioe?aeo, oae ? a?ae iicaee?oeiii? eiioeaio?aoe?? ?ii?a.
Iioaioe?ae eaiaeo iiaeeco a?ae/eiaiiai (x1) oa ca/eiaiiai (x3) noai?a ie
iiaeaii caaeaoe o aeaeyae? ia?aaie:

I(o)=a?o2+a?o+eOn?(, o?-(? ( o ( o?+(? (2)

aea ?=1 aai 3, ( — iaia?aiiee iioaioe?ae, ai, bi oa ci — oea o?eniaai?
no?oeoo?i? ia?aiao?e eaiaeo, (? — iiceoeaia aaee/eia, ui aecia/a?
a?aeoeeaiiy a?ae i?i?ioio xi, eiee a??ia iaaeeaeaiiy (2).

Aeei?enoiaoth/e aca?iicaeaaei?noue tn, n(, ( oa ( (tn=1/(((, n(=(((((),
ie ia/eneeee caeaaei?noue ( oa ( a?ae [K+]cia (?en.6). Caeaaei?noue a
a?ae [K+] ia? a?eueo ae?aciee oa?aeoa?, i?ae aeey b, ui icia/a?, ui
??cieoey U(x1)-U(x2) ? iino?eiith, a cia/aiiy U(x3)-U(x2) caeaaeeoue
a?ae [K+]cia. A?aee?eoee noai (x1) i?aeoe/ii ia/ooeeaee aei
iicaee?oeiii? [K+]. A oie aea /an aeno?aioie caeaaeiinoae a a?ae [K+]cia
ia cnoaaeeny aeey ??cieo cia/aiue iaia?aiiiai iioaioe?aeo.

Oaeei /eiii, iaia?aiiee iioaioe?ae ia aieeaaa ia ?EA. Oea iiaea cia/eoe,
ui aoaeoe, ui niinoa??aathoueny, aecia/athoueny caeaaei?noth canaeaiiy
eaiaeo a i?noe?, aeecueeiio aei ciai?oiueiai ?ic/eio. Caaaeyee a?eueo
oaeaeeiio iai?io ?c ciai?oi?i ?ic/eiii, canaeai?noue a i?noe?
ca’ycoaaiiy aecia/a?oueny a iniiaiiio iicaee?oeiiith eiioeaio?aoe??th
?ii?a eae?th, a ia iioaioe?aeii oa/aai aioo??oiueith ?o
eiioeaio?aoe??th.

Ioaea, aa?o/e aei oaaae, ui [K+]cia i?aeoe/ii ia ci?ith? oaeaee?noue
ia?aoiaeo (, ciaooo?ii V(x) i?e ?icaeyae? a?aee?eoiai noaio (x1). Aeey
i?inoioe aoaeaii ?icaeyaeaoe iieiaeaiiy x2 oa cia/aiiy U(x2) o?eniaaiei
(U(x2)=const), oiaoi o?eueee iioaioe?ae, ui aecia/a? ca/eiaiee noai
(x3), /ooeeaee aei ci?i [K+]cia, ui iaoiiaeth?oueny iaeaaei?noth
ooieoe?? V(x) a ?EA. Iiaeaii ciiao ni?inoeoe, aaaaeath/e, ui
?ii-eiioi?iaoe?eia neea ? iino?eiith, oiaoi dV(x)/dx=(N, aea N — oea
canaeai?noue, ui ? aieiaiei o?ce/iei ia?aiao?ii, ui aecia/a? ?EA, a ( —
oea neea, ui ae??, eiee ?ii iino?eii ciaoiaeeoueny eaiae? (N=1). ?EA
i?iii?oe?eia /eneo ?ii?a, ui i?eeiathoue o/anoue o aca?iiae??, oiaoi N.
?ioaa?oth/e ii o, io?eio?ii iioaioe?ae V(x):

V(x)= (Nx + (N, x3 — (3 ( o ( o3+(3 (3)

aea iino?eia ?ioaa?oaaiiy (N i?iii?oe?eia N. A oeueiio aeiaaeeo ye
?ii-eiioi?iaoe?eia neea, oae ? aia?a?y aei??aith?oueny ioeth, eiee
i?noea ca’ycoaaiiy a?eueia (N=0). Oaeei /eiii, eiioi?iaoe?eiee
iioaioe?ae U(x) iiaeeeai iienaoe o a?ae/eiaiiio noai?:

U(x)=a1x2 + b1x + kTc1(, x1 — (1 ( o ( o1+(1 (4a)

oa a ca/eiaiiio noai?:

U(x)=a3x2 + (b3 + (N)x + kTc3( + (N, x3 — (3 ( o ( o3+(3 (4a)

Ca oiia, ui aecia/athoue iieiaeaiiy i?i?ioi?a x1 oa x3 dU(x)/dx=0
aeaeii, ui ca/eiaiee noai aecia/a?oueny ye o3= -(b3+(N)/2a3 oa,
i?aenoaaeyth/e oeae ae?ac a ??aiyiiy (4a), io?eio?ii cia/aiiy
eiioi?iaoe?eiiai iioaioe?aeo U(x) a oe?e oi/oe?:

U(x3) = kT( -k(N — N0)2 + c3(( + U30 (5a)

aea eiinoaioe (, N0 oa U30 aecia/athoueny iiia?aaei?ie ia?aiao?aie a3,
b3, ( oa (, ye? caeaaeaoue a?ae iioaioe?aeo; N0 aecia/a? iieiaeaiiy
aeno?aioio U(x3) oa, ioaea, aeno?aioio eiinoaioe oaeaeeino?. Oaeei
/eiii, oey oi?ioea i?eionea?, ui iaeneioi ooieoe?? (([K+]ia?) ia
caeaaeeoue a?ae iaia?aiiiai iioaioe?aeo, ui ? niinoa??aa?oueny a
aenia?eiaio?.

A oie aea /an aia?a?y U(x) a iieiaeaii? x1 iiaea aooe caienaia o
aeaeyae?:

(5a)

I?aenoaaeyth/e ae?ace (5) a ??aiyiiy (1) ? aaiaey/e iia? ia?aiao?e,
ciaeaeaii eiinoaioe oaeaeeino?:

(=(0exp(-k(N-N0)2 +c3((, (=(0exp(c1(( (6)

aea (0 oa (0 — iia? ia?aiao?e iiaeae?, ye? aeeth/athoue ii/aoeia?
aia?a?? Ui0. Caoaaaeeii, ui an? ia?aiao?e iiaeae? a ??aiyii? (6) ?
aca?iii iacaeaaeieie ? iiaeeeai ai?ieneioaaoe ( oa ( iacaeaaeii.

Oaeei /eiii, eiioi?iaoe?eiee iioaioe?ae, ui aecia/a? e?iaoeeo eaiaeo ii
??aiyiith (1), caeaaeeoue a?ae eaaae?aoo canaeaiino? N. Oey caeaaei?noue
aecia/a? iae?i?eiino?, iaaaaeai? ia ?enoieao 3 ? 5. I/aaeaeii, ui
c?inoaiiy eiioeaio?aoe?? aeeeeea? c?inoaiiy canaeaiino? N, iiee ia aoaea
aeinyaiooa iane/aiiy, ui iaoiiaeaia iaiaaeaiei ?ici??ii i?noey
ca’ycoaaiiy a eaiae?, oae ui N ia iiaea ia?aaeueoe a?aie/io aaee/eio.

IAAIAI?AIIss

A ea?ae?ii?ioeeoao, aeeoa?aioe?eiaaieo in vitro c aia??iiaeueieo
noiaao?iaeo ee?oei, iniiaiei ?aiiey?ecoth/ei no?oiii aoa E+ no?oi, ui
oaeaeei aeoeao?oueny. Ie aeae?eeee o?e ??cieo eiiiiiaioe no?oio, aianie
yeeo a noia?iee no?oi caeaaeaa a?ae a?eo ee?oei. Oe? eiiiiiaioe
a?ae??ciyeeny ye ii e?iaoeoe?, oae ? ii /ooeeaino? aei iicaee?oeiiiai
i?eeeaaeaiiy ai?iii???ae?i?a. Oaeaeeee eae??aee no?oi (Ito) aoa
i?enooi?e i?aeoe/ii o an?o i?ioanoiaaieo ea?ae?ii?ioeeoao, aea eiai
aeaeo?io?c?ieia?/ia ?ieue (noia?iee ca?yae, ui ia?aiineany ca /an
oanooth/iai ci?uaiiy iioaioe?aeo) aoea a?eueo ae?acia a ee?oeiao
?aiiuei? noaae?? aeeoa?aioe?thaaiiy. Aonoeia oe??? eiiiiiaioe no?oio
eeoa iacia/ii c?inoaea a i?ci?o ea?ae?ii?ioeeoao. A oie aea /an aonoeia
eiiiiiaioe, ui ia?iaeoeao?oueny, aoea ia oae nooo?aa, ye aonoeia Ito
eiiiiiaioe. A i?ci?o ee?oeiao aonoeia Isus ca?eueooaaeany a?eueo i?ae a
aeaa ?ace. Aa?o/e aei oaaae i?aeoe/io a?aenooi?noue ?iaeoeaaoe?? oeueiai
no?oio, eiai aeaeo?io?c?ieia?/ia ?ieue cia/ii c?inoaea a
ea?ae?ii?ioeeoao i?ciuei? noaae?? aeeoa?aioe?thaaiiy. Ie ae?eoee
aeniiaeo, ui a ?aii?o ea?ae?ii?ioeeoao Ito-iiae?aia eiiiiiaioa no?oio ?
iniiaiith a eiio?ie? aeaeo?e/ii? aeoeaiino? ee?oei, a a i?ci?o
ea?ae?ii?oeeoao neeueii i?aeaeuo?oueny ?ieue 4-AI ia/ooeeai? eiiiiiaioe
no?oio (Isus). A /anoei? ee?oei, ui aoee i?ioanoiaai? (aeecueei 30%),
aoea i?enooiy ua e a?ia?/ooeeaa eiiiiiaioa no?oio c iia?eueiith
?iaeoeaaoe??th. Ia iaoo aeoieo, oeae no?oi ia ia? nooo?aiai cia/aiiy a
noaa?e?caoe?? /anoioe aaia?aoe?? IAe, aea aaaeeeaee aeey ?aaoethaaiiy
neee oa o?eaaeino? nei?i/aiiy ee?oei i?iea?aeo.

A i?ioean? ?iaioe c ea?ae?ii?ioeeoaie, aeeoa?aioe?eiaaieie in vitro, ie
?iiae? niinoa??aaee ia/eiaee oei aeaeo?e/ii? aeoeaiino? ee?oei.
Iicaee?oeii? ?a?no?aoe?? a?ae ae?eyiie, ui nei?i/oaaeenue, aeacoaaee ia
AOO-/ooeea? K+ eaiaee, ye ia eaiaee, ui aecia/aee oeae oei aeaeo?e/ii?
aeoeaiino? ee?oei. Aeiaeaaaiiy a iicaee?oeiiee ?ic/ei aeieaoi?o IE,AOO
ae?aaieeai?aeo ia?aoai?thaaei ia/eiao aeoeai?noue a cae/aei? ?aaoey?i?
?eoi?/i? nei?i/aiiy. Ia/eiaa aeoeai?noue eaaei aeeeeeaeanue ciaioaiiyi
ai?noo iaoaaie?/ieo eiiiiiaio?a a eoeueoo?aeueiiio na?aaeiaeu?, ui
aeaco? ia ca’ycie i?ae iaoaaie?/iei noaiii aia??iiaeueiiai o?eueoey oa
iaia?aiiith caoaeeea?noth ea?ae?ii?ioeeo?a. ??cieoey a aia?aaoe/iiio
aaeain? oa eiai i?aeo?eiaii? iiaea iiynieoe niiioaiio aeaeo?e/io
aeoeai?noue aia??iiaeueieo o?eaoeue a eoeueoo?aeueiiio na?aaeiaeu? oa
o?eaoeue, ui aoee aeayeee /an a iicaee?oeiiiio ?ic/ei?.

Eieeaaeuei? ci?ie, aea ia ia/eiaa iiaaae?iea iaia?aiii? caoaeeeaino?
aaea aoee ?ai?oa iieacai? o aaio?eeoey?ieo ea?ae?ii?ioeeoao (O’Rourke,
et al., 1994). Oeeee?/i? ci?ie aeoeaiino? AAeO oa IAAeI ci?ithaaee
iaia?aiio caoaeeea?noue oeyoii ae?? ia eaiaee IE,AOO. Oaeiae a?aeiii, ui
aeoeai?noue eaiae?a IE,AOO neeueii caeaaeeoue a?ae eiioeaio?aoe?? AAeO.
I?noea ca’ycoaaiiy AAeO ?icoaoiaaia ia ?aoeaioi?? SUR, ? ca’ycoaaiiy
AAeO caaaaea? aeieo AOO, yeee iiaea aeieeaoe aaciina?aaeiuei ia eaiae?
KIR 6.2. Oea i?eionea?, ui i?ioeane, ye? iio?aaothoue i?enooiino? AOO, a
ea?ae?ii?ioeeoao a iniiaiiio i?aeo?eiothoueny AOO, io?eiaiei a oiae?
ae?eie?co. I?yia /e iai?yia aeeth/aiiy i?oioiiae??aeueieo eieeaaiue ia
iiaea aooe iiai?noth aeeeth/aii aeey iaoi? nenoaie, aea aiii
iaeieiia??ii, oae ye ia/ee aeieeaee niiioaiii oa iiaee aooe aeeeeeai? a
i?enooiino? iicaee?oeiiiai aethoaiaoo oa i??oaaoo — ?a/iaei, ye?
iiaeooue aeei?enoiaoaaoenue i?oioiiae??yie a ieenethaaeueiiio
iaoaaie?ci?.

Ie c?iaeee ni?iao ?ice?eoe o?ceei-o?i?/i? iaoai?cie ooieoe?iioaaiiy
iaea?eueo nooo?aiai oeio ?iiieo eae??aeo eaiae?a — eaiae?a Ito no?oio.
Aii??e/ia oai??y e?iaoeee ?iiieo no?oi?a Oiaeaee?ia-Oaene? caniiaaia ia
e?iaoe/ieo ??aiyiiyo, ui ca’ycothoue no?oi e??cue iaia?aio c aeaeo?e/iei
iioaioe?aeii. Oey iiaeaeue iaaea? caaeia?eueiee iaoaiaoe/iee iien
iiaaae?iee iaia?ai, ui caoaeaeothoueny, oa iaaea? iai/ia oyaeaiiy i?i
ooieoe?iioaaiiy ?iiiiai eaiaeo. Aea oey oai??y ia ciiaea aeaoe ei?aeoio
iae?ineii?/io ?ioa?i?aoaoe?th ai?ioieo i?ioean?a. E??i oiai, oey
iiaeaeue ia iieno? eiioeaio?aoe?eieo caeaaeiinoae ia?aiao??a ?iiieo
no?oi?a. Iai?eeeaae, niinoa??aaeanue iae?i?ei?noue aieueo-aiia?ii?
oa?aeoa?enoeee iiiaeeiieiai eaiaeo i’yc?a ethaeeie (Fahlke &
Ruppersberg, 1998). Aoei iieacaii, ui iao???aee no?oi i?e iioaioe?ae?
+130 iA ? iae?i?eiith ooieoe??th ciai?oiuei? eiioeaio?aoe?? ?ii?a
iao??th, oi/a aeaeo?io?i?/iee a?aae??io iiaeiai /eieoe i?ioeeaaeiee
aoaeo. Aoei iieacaii, ui no?oeoo?a iioaioe?aeueiiai i?io?eth eaiaeo
ci?ith?oueny a caeaaeiino? a?ae eiioeaio?aoe?? ?ii?a, ui i?ioiaeyoue
e??cue eaiae (Eisenman & Dani, 1986). Cnoa caeaaeiinoae e?iaoe/ieo
oa?aeoa?enoee oa no?oi?a a?ae iioaioe?aeo a noi?iio iioaioe?aeo ?aaa?n??
a?aeia?aaeathoue aieea ?iiieo eiioeaio?aoe?e ia e?iaoeeo eaiaeo (Hille,
1992; White et al., 1993). Oe? oaeoe, ye ? aaaaoi ?ioeo, aeacothoue, ui
eiioeaio?aoe?y ?ii?a iiaea eiio?iethaaoe ooieoe?iioaaiiy eaiaeo.
Aeei?enoaiiy o?ioe ?ioiai i?aeoiaeo aei iieno ?EA (Kharkyanen et al.,
1994; Weinreb & Kharkyanen, 1995) aeicaiey? ae??oeoe oe? i?iaeaie: cnoa
n((() i?e ci?iao ?iiieo eiioeaio?aoe?e, cieeiaiiy ca/eiaiiai noaio i?e
ioeueiaiio no?oi?, i?e?iaeo eiioi?iaoe?eieo noai?a eaiaeo oa ?io?. Oaeee
i?aeo?ae aeicaiey? iienaoe ? iao? aenia?eiaioe. Ie aa/eii, ui
iaiiiioiii? caeaaeiino? oaeaeeinoae ia?aoiae?a i?ae noaiaie a?ae
iicaee?oeiii? eiioeaio?aoe?? eae?th ca’ycai? c aeaoi?iaoe??th
aoaeoeaiiai eiioi?iaoe?eiiai iioaioe?aeo U(x). Oaeei /eiii, iao?
?acoeueoaoe i?aeoaa?aeaeothoue oi/eo ci?o, ui ?ii-eioi?iaoe?eia
aca?iiae?y iiaea cia/ii aieeaaoe ia ooieoe?iioaaiiy eaiaeo.

AENIIAEE

Aeine?aeaeaii eae??aee no?oi, ui aeoiaeeoue a ea?ae?ii?ioeeoao,
aeeoa?aioe?eiaaieo c aia??iiaeueieo noiaao?iaeo ee?oei, yeee iiaeeeai
?icae?eeoe ia o?e ??ci? eiiiiiaioe ii e?iaoeoe? aeoeaaoe?? oa
?iaeoeaaoe?? oa aeei?enoiaoth/e ?o ??cio /ooeea?noue aei
ai?iii???ae?i?a.

I?ine?aeeiaaii ci?ie aonoeie o?ueio eiiiiiaio eae??aiai no?oio, ui
aeoiaeeoue, a naia: Ito — oaeaeeiai o?aic??ioiiai, Islow, ui iia?eueii
?iaeoeao?oueny oa Isus, ui ia?iaeoeae?oueny, a?ae a?eo ea?ae?ii?ioeeo?a
a i?ioean? ?aiiueiai ea?ae?ii?iaaiaco.

Ia ?aii?o ia??iaeao aeeoa?aioe?thaaiiy iniaeeai aaaeio ?ieue a?ae?a?a?
eiiiiiaio eae??aiai no?oio, ui oaeaeei ?iaeoeao?oueny — Ito no?oi, yeee
ia o?eueee i?eeia? o/anoue a oi?ioaaii? iioaioe?aeo ae??
ea?ae?ii?ioeeo?a, a ? a?ae?a?a? aaaeeeao ?ieue a noaa?e?caoe??
aeaeo?e/ii? aeoeaiino? ee?oeie.

AOO-caeaaei? eae??a? eaiaee a?ae?a?athoue aaaeeeao ?ieue ia an?o
ia??iaeao ?aiiueiai ea?ae?ii?iaaiaco ? ? oaeeie, ui iaoiiaeththoue
aeieeiaiiy ia/eiaiai oeio aeaeo?e/ii? aeoeaiino? ea?ae?ii?ioeeo?a.

Aiae?c e?iaoe/ieo oa?aeoa?enoee oaeaeeiai eae??aiai no?oio iieacaa, ui
ci?ia iicaee?oeiii? eiioeaio?aoe?? ?ii?a eae?th aaaea aei ?o ci?ie, ye?
iaaii iaoiiaeaii? iaeaaei?noth ?ii-eiioi?iaoe?eii? aca?iiae?? ?ii?a ?c
no?oeoo?ith eaiaeo.

?iaioe, iioae?eiaai? ca iaoa??aeaie aeena?oaoe??

A?euaiei A.A., Aa?acaoneay I.I., Aaei?aa A.A., Eiiiiaiei I.E., Naaeiaa
I.A. Aeeyiea aiaeeaoi/iie eiioeaio?aoeee eiiia eaeey ia
ooieoeeiie?iaaiea iioaioeeae caaeneiuo eaeeaauo eaiaeia eeaoie GH3 //
Iae?ioeceieiaey.-1995.- O.27.- N2.- N.85-89.

O.V.Grishchenko, V.N.Kharkyanen, N.I.Kononenko and G.E.Weinreb. Ion
Regulation of the Kinetics of Potential-Dependent Potassium Channel //
Journal of Biological Physics.- 1997.- V.23.- P.195-208.

A?euaiei A.A. Eciaiaiey yeni?annee eiiiuo eaiaeia a ea?aeeiieioeeoao
ieaeiieoathueo ai a?aiy ?aiiaai yia?eiaaiaca //
Iae?ioeceieiaey.-1998.-O.30. N3.-C.232-237.

Oace aeiiia?aeae:

First meeting of the German-Ukrainian Research Group, Ee?a, 1996.
Gryshchenko O.V., Outward rectifier K+ channels in cardiomyocytes:
Control by development and long-term application of blockers.

Deutsche Physiologische Gesellschaft, 76th Annual Meeting, Rostock,
Germany, 1997. Gryshchenko O.V., Fleischmann B.K., Hescheler J. Outward
rectifier K+ currents in early- and late stage cardiomyocytes derived
from embryonic stem cells.

Deutsche Physiologische Gesellschaft, 76th Annual Meeting, Rostock,
Germany, 1997. Igelmund P., Fischer I.R., Soest J., Gryshchenko O.V.,
Fleischmann B.K., Hescheler J. Nimodepine induces arrhythmia in
cardiomyocyte clusters in three-dimensional cell culture.

Deutsche Physiologische Gesellschaft, 76th Annual Meeting, Rostock,
Germany, 1997. Gryshchenko O.V., Fischer I.R., Soest J.,
Viatchenko-Karpinski S., Igelmund P., Fleischmann B.K., Hescheler J.
Bursting behavior induced by ATP-sensitive K+ channels in embryonal stem
cell derived cardiomyocytes.

Conference on Physics of Biological Systems, Ee?a, 1998. Gryshchenko
O.V., Weinreb G.E. Nonlinear effects of ion-conformational interaction
in potassium channels of biomembranes.

AIIOAOe??:

A?euaiei I.A. Aeine?aeaeaiiy eae??aeo eaiae?a oa ?o ?ie? a
ea?ae?ii?ioeeoao, aeeoa?aioe?eiaaieo c aia??iiaeueieo noiaao?iaeo ee?oei
ieo?. — ?oeiien.

Aeena?oaoe?y ia caeiaoooy iaoeiaiai nooiaiy eaiaeeaeaoa 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, 1998.

Ca aeiiiiiaith iaoiaeo o?enaoe?? iioaioe?aeo aoei aeine?aeaeaii eae??aee
no?oi iaia?aie iiiaeeiieeo ea?ae?ii?ioeeo?a, aeeoa?aioe?eiaaieo in vitro
c aia??iiaeueieo noiaao?iaeo ee?oei ieo? e?i?? D3. Iieacai? ci?ie
aeni?an?? eae??aeo eaiae?a ee?oei i?ae /an ?aiiueiai ea?ae?ii?iaaiaco.
Iieacaia iniaeeai aaaeeeaa ?ieue eaiae?a o?aic??ioiiai no?oio (Ito) a
oi?ioaaii? oa i?aeo?eioe? noaa?eueii? aeaeo?e/ii? aeoeaiino?
ea?ae?ii?ioeeo?a ia ?aiiueiio no?ieo aeeoa?aioe?thaaiiy — a?ae aeaio aei
/ioe?ueio ae?a i?ney iiyae niiioaiieo ?eoi?/ieo nei?i/aiue. Anoaiiaeaii,
ui ia a?aei?io a?ae ?ioeo oei?a eae??aeo eaiae?a, AOO-caeaaei? eaiaee
aeni?anothoueny i?aeoe/ii o an?o ea?ae?ii?ioeeoao iacaeaaeii a?ae no?ieo
aeeoa?aioe?thaaiiy ? aonoeia IK,AOO i?aeoe/ii ia ci?ith?oueny c a?eii
ee?oei. Iieacaia ?ieue AOO-caeaaeieo eaiae?a a ci?iao aeaeo?e/ii?
aeoeaiino? ea?ae?ii?ioeeo?a, ui aeieeathoue i?e ci?iao aia?aaoe/iiai
iaoaaie?cio ee?oeie. Aecia/ai? iaoai?cie aieeao iicaee?oeiii?
eiioeaio?aoe?? K+ ia ooieoe?iioaaiiy eae??aeo eaiae?a oaeaeeiai
o?aic??ioiiai no?oio, ui iaoiiaeai? ?ii-eiioi?iaoe?eiith aca?iiae??th
a?eeo, ui oi?io? eaiae, oa ?ii?a, ui i?io?eathoue e??cue iueiai.

Eeth/ia? neiaa: ea?ae?ii?ioeeoe, K+ eaiaee, AOO-caeaaei? eaiaee,
?ii-eiioi?iaoe?eia aca?iiae?y.

A?euaiei A.A. Enneaaeiaaiea eaeeaauo eaiaeia e eo ?iee a
ea?aeeiieioeeoao, aeeooa?aioee?iaaiiuo ec yia?eiiaeueieo noaieiauo
eeaoie iuoe. — ?oeiienue.

Aeenna?oaoeey ia nieneaiea o/aiie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe
ii niaoeeaeueiinoe 03.00.02-aeioeceea. — Einoeooo oeceieiaee ei.
A.A.Aiaiiieueoea IAI Oe?aeiu, Eeaa, 1998.

N iiiiuueth iaoiaea oeenaoeee iioaioeeaea enneaaeiaaeny eaeeaaue oie
iaia?ai iaeeii/iuo ea?aeeiieioeeoia, aeeooa?aioee?iaaiiuo in vitro ec
yia?eiiaeueiuo noaieiauo eeaoie iuoe eeiee D3. Iieacaiu eciaiaiey
yeni?annee eaeeaauo eaiaeia eeaoie ai a?aiy ?aiiaai ea?aeeiieiaaiaca.
Iieacaia iniai aaaeiay ?ieue eaiaeia auno?iai o?aiceaioiiai oiea (Ito) a
oi?ie?iaaiee e iiaeaea?aeea noaaeeueiie yeaeo?e/aneie aeoeaiinoe
ea?aeeiieioeeoia ?aiiaai n?iea aeeooa?aioee?iaaiey — io aeaoo aei
/aou?ao aeiae iinea iiyaeaiey niiioaiiuo ?eoie/aneeo nie?auaiee.
Onoaiiaeaiii, /oi a ioee/ee io ae?oaeo oeiia eaeeaauo eaiaeia,
AOO-caaeneiua eaiaeu yeni?anne?othony i?aeoe/anee ai anao
ea?aeeiieioeeoao iacaaeneii io n?iea aeeooa?aioee?iaaiey e ieioiinoue
IK,AOO i?aeoe/anee ia eciaiyaony n aic?anoii eeaoie. Iieacaia ?ieue
AOO-/oanoaeoaeueiuo eaiaeia a eciaiaieyo, aicieeathueo i?e eciaiaieyo
yia?aaoe/aneiai iaoaaieecia eeaoee. Ii?aaeaeaiu iaoaieciu aeeyiey
aiaeeaoi/iie eiioeaio?aoeee K+ ia ooieoeeiie?iaaiea eaeeaauo eaiaeia
auno?iai o?aiceaioiiai oiea, iaoneiaeaiiua eii-eiioi?iaoeeiiiui
acaeiiaeaenoaeai eaiaeiia?acoauaai aaeea e i?iieeathueie eiiie.

Eeth/aaua neiaa: ea?aeeiieioeeou, K+ eaiaeu, AOO-caaeneiua eaiaee,
eii-eiioi?iaoeeiiiia acaeiiaeaenoaea.

Gryshchenko O.V. Enneaaeiaaiea eaeeaauo eaiaeia e eo ?iee a
ea?aeeiiioeeoao, aeeooa?aioee?iaaiieo ec aia?eiiaeueieo noaieiaeo eeaoie
ieoe. — ?oeiienue.

Thesis for a candidate’s degree by speciality 03.00.02 — biophysics.-
Bogomoletz Institute of Physiology of the National Academy of Sciences
of Ukraine, Kyiv, 1998.

Path-clamp technique has been used to investigate potassium currents in
the membranes of single cardiomyocytes differentiated in vitro from
embrionic stem cells (D3 line). Changes in the expression of potassium
channels in early cardiomyogenesis have been shown. A significant role
of the channels of rapid transient current (Ito) has been proved in
forming and maintaining the stable electric activity of early
cardiomyocytes — from two to four days after the spntaneous contractions
begin. It has been found that unlike other types of potassium channels,
ATP-dependent channels are expressed practically in all cardiomyocytes
irrespective of the differentiation time, and that the density of IK,ATP
practically does not change at different stages. The role of
ATP-sensitive channels in variations that occur with the change of
energy metabolism of a cell has been shown. The mechanisms of the
influence of outside K+ concentration on the functioning of potassium
channels of the rapid transient current caused by ion-conformational
interaction of channel-forming protein with passing ions have been
determined.

Key words: cardiomyocytes, K+ channels, ATP-sensitive channels,
ion-conformational interaction.

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