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

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

(((((((((((((((((((((((((((((

Aaneeue?a Aeieo?i Aaneeueiae/

OAeE 612.822:577.352.5

Iioaioe?aeaeoeaiaai? eae??a? no?oie iae?ii?a ni?iaeueieo aaiae??a oa
a?iieaiio uo??a: iioiaaiac ? ?ieue o aaeuei?ai?e neiaioe/i?e ia?aaea/?

03.00.02 — a?io?ceea

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?aeia?iaeiee Oeaio? iieaeoey?ii?
o?c?ieia?? IAIO,

canooiiee aee?aeoi?a ii iaoeia?e
?iaio?

Io?oe?ei? iiiiaioe:

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

Eaiaeeaeao a?ieia?/ieo iaoe, noa?oee iaoeiaee ni?a?ia?oiee ?inoeoooo
o?c?ieia?? ?i. I. I. Aiaiiieueoey Eiciaa
Iaoae?y Aeaen??aia

I?ia?aeia onoaiiaa:

Eaoaae?a a?io?ceee Iaoe?iiaeueiiai Oi?aa?n?oaoo ?i. O. A. Oaa/aiea

Caoeno a?aeaoaeaoueny “23“ ethoiai 1999 ?. i 14 aiaeei? ia can?aeai?
niaoe?ae?ciaaii? a/aii? ?aaee Ae-01.13.01 i?e ?inoeooo?
o?c?ieia??

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

Aaoi?aoa?ao ?ic?neaiee “22“ n?/iy 1999 ?.

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

Aeine?aeaeaiiy iioaioe?aeea?iaaieo eae??aeo eaiae?a iae?iiaeueieo ee?oei
a iei?oi?e /an i?eaa?oathoue c?inoath/o oaaao. Oea aecia/a?oueny
aaaeeeaith ?ieeth eaiae?a eae??aiai no?oio a ?aaoeyoe?? caoaeeeaino?
iae?ii?a, aeeth/ath/e ni?iiiaei?noue ?ioaa?oaaoe neiaioe/i? neaiaee,
ci?ithaaoe ?ao?aeoa?iee ia??iae, aecia/ath/e /anoioo aaia?aoe??
iioaioe?ae?a ae??, a oaeiae iiaeoethaaoe o?eaae?noue oa oi?io ie?aiiai
iioaioe?aeo ae?? a ia?aiaeo oa?i?iaeyo, aieeaath/e caaaeyee oeueiio ia
aeeeae iae?iiaae?aoi?o (Thompson and Aldrich, 1980; Adams and Galvan,
1986). Oe? ?ioaa?aoeai? aeanoeaino? eae??aeo no?oi?a aecia/athoueny
?oi?ie niaoeeo?/ieie ia?aiao?aie: ??aiai noaoe?iia?ii? ?iaeoeaaoe??
eae??aeo eaiae?a i?e iioaioe?ae? niieith ee?oeie, ii?iaii ?oiuei?
aeoeaaoe??, oaeaee?noth ?iaeoeaaoe??, a oaeiae u?euei?noth no?oio.

Aeine?aeaeaiiy iioaioe?aeea?iaaieo eae??aeo no?oi?a oeaio?aeueieo
iae?ii?a nnaaoe?a anoaiiaeee aeiaie? niaoeeo?/io iine?aeiai?noue ci?i
u?eueiino? eae??aeo no?oi?a a ia??iae ?aiueiai iioiaaiaco (Barish, 1995;
Klee et al., 1995). O?c?ieia?/ia ?ieue oaeeo i?ioean?a oa ?o iniaeeaino?
a ??cieo ae?eyieao ia?aiai? nenoaie ua ia aei e?ioey aeyaeai?. A?eueo
oiai, aeine?aeaeaiiy ci?i eae??ai? i?ia?aeiino? iae?ii?a ia?eoa?e/ii?
ia?aiai? nenoaie, cie?aia iae?ii?a ni?iaeueieo aaiae??a, ia nueiaeiyoi?e
iiiaio ia i?iaiaeeeeny. Iiaeeo?eaoe?? eae??ai? i?ia?aeiino?
iae?iiaeueii? iaia?aie iiaeooue a?ae?a?aaaoe noooaao ?ieue a ?aaoeyoe??
aeeoo?ae?yeueiino? ye ie?aii? ee?oeie oae ? oe?eeo iae?iiieo eiiieaen?a.
Oae, ooieoe?iiaeueia ?ieue eae??aeo eaiae?a a iae?iiao a?iieaiio
ca’yco?oueny c ?oiueith ni?iiiaei?noth iiaeoethaaoe ia/a/io aeoeai?noue
iae?ii?a a?iieaiio (Nakajima et al., 1986; Segal et al., 1984; Storm,
1987; Wu and Barish, 1992). Aie?eaoe?y i?e?iiiey?ieo eiioeaio?aoe?e 4-AI
i?ecaiaeeea aei niiioaiieo ai?eaioe/ieo ?ic?yae?a a i?aia?aoao c??c?a
a?iieaiio, ui aoei iiyniaia ca?eueoaiiyi aeeeaeo iae?iiaae?aoi?o a
?acoeueoao? i?aeaeuaiiy ??aiy aeaiiey?ecaoe?? i?aneiaioe/ieo oa?i?iaeae
(Rutecki et al., 1987). OAA a eiioeaio?aoe?? 25 iI aeeeeeaa
Na++-caeaaeio, aea NMDA-iacaeaaeio aeieaio?eaaeo iioaioe?aoe?th
neiaio/ii? ia?aaea/? NA1 iaeano? a?iieaiio uo??a (Aniksztejn and
Ben-Ari, 1991). Iaeiae, iaoai?ci aieeao aeieaoi??a eae??aeo eaiae?a ia
neiaioe/io ia?aaea/o iae?ii?a nnaaoe?a oaeoe/ii caeeoa?oueny ia
c’yniaaiei. Ca?eueoaiiy iinoneiaioe/ii? a?aeiia?ae? i?ae aieeaii
aeieaoi??a eae??aeo eaiae?a iiaea aooe coiiaeaia ye aoyaiaiiyi
aeiaeaoeiai? e?eueeino? ooieoe?iioth/eo oa?i?iaeae oae ? ca?eueoaiiyi
aeeeaeo iae?iiaae?aoi?o c ie?aii? neiaioe/ii? oa?i?iae?. Oaeei /eiii,
aeine?aeaeaiiy aieeao ci?ie eae??ai? i?ia?aeiino? ia neiaioe/io
ia?aaea/o oeaio?aeueieo iae?ii?a nnaaoe?a ? aeooaeueiei ? iiaei aeey
?icoi?iiy ooiaeaiaioaeueieo iaoai?ci?a neiaioe/ii? ia?aaea/? iae?ii?a
OeIN.

Iaoa aeine?aeaeaiiy

Aecia/eoe aeanoeaino? iioaioe?aeea?iaaieo eae??aeo no?oi?a iae?iiaeueii?
iaia?aie naini?ieo ? oeaio?aeueieo iae?ii?a ia ?aii?o noaae?yo
iioiaaiaco oa c’ynoaaoe iaoai?ci aieeao ci?i eae??ai? i?ia?aeiino?
i?aneiaioe/ii? iaia?aie ia neiaioe/io ia?aaea/o.

Caaaeaiiy aeine?aeaeaiiy

1. Aeeiiaoe ?iciiae?e oa ?aeaioeo?eaoe?th ??cieo oei?a
iioaioe?aeea?iaaieo eae??aeo no?oi?a niiaoe/ii? iaia?aie iae?ii?a
ni?iaeueieo aaiae??a ? a?iieaiio uo??a. Ia iniia? io?eiaieo aeaieo
c?iaeoe ii??aiyeueiee aiae?c eae??ai? i?ia?aeiino? niiaoe/ii? iaia?aie
aeaio oei?a iae?ii?a.

2. Aeine?aeeoe ci?ie u?eueiino? ??cieo oei?a iioaioe?aeea?iaaieo
eae??aeo no?oi?a niiaoe/ii? iaia?aie iae?ii?a ni?iaeueieo aaiae??a
i?ioyaii ia?oeo aeaio oeaei?a iinoiaoaeueiiai ?icaeoeo.

3. Aeei?enoiaoth/e iaoiae iicaee?oeiii? aeaeo?e/ii? noeioeyoe?? a oiiaao
a?aenooiino? aaia?aoe?? iioaioe?aeo ae?? (a ?ic/ei?, ui i?noeoue
oao?iaeioien?i, OOO), aeine?aeeoe aieea aeieaoi??a iioaioe?aeea?iaaieo
eae??aeo eaiae?a ia aaeuei?ai? iinoneiaioe/i? no?oie ie?aieo neiaioe/ieo
oa?i?iaeae iae?ii?a a?iieaiio.

Iaoeiaa iiaecia ?iaioe

C?iaeaia ?aeaioeo?eaoe?y ??cieo oei?a iioaioe?aeea?iaaieo eae??aeo
no?oi?a a iae?iiao ni?iaeueieo aaiae??a ? a?iieaiio uo??a. Aeine?aeaeai?
ci?ie u?eueiino? eae??aeo no?oi?a naini?ieo iae?ii?a uo??a a ?aiiueiio
iinoiaoaeueiiio ia??iae?.

Aia?oa iieacaii, ui ca?eueoaiiy aoaeoeaiino? aaeuei?aii? neiaioe/ii?
ia?aaea/? oeaio?aeueieo iae?ii?a nnaaoe?a i?ae aieeaii aeieaoi??a
eae??aeo eaiae?a coiiaeth?oueny ca?eueoaiiyi na?aaeiueiai eaaioiaiai
ai?noo aeeeaeo iae?iiaae?aoi?o c ie?aii? neiaioe/ii? oa?i?iae?.

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

Io?eiai? i?eioeeiiai iia? aeai? i?i iaoai?ci ae?? aeieaoi??a eaee?aeo
eaiae?a ia aeeeae iae?iiaae?aoi?o a aaeuei?aiiio neiaioe/iiio cae?i/aii?
iae?ii?a a?iiieaiio uo??a. Ci?ie eae??ai? i?ia?aeiino? i?aneiaioe/ii?
iaia?aie ye a i?ioean? iioiaaiaoe/iiai ?icaeoeo, oae ? i?ae aieeaii
ciai?oi?o oaeoi??a iiaeooue a?ae?a?aaaoe ia?oi?yaeio ?ieue a iaoai?ciao
neiaioe/ii? ieanoe/iino?.

Iniaenoee aianie

Aaoi?ii iniaenoi aoee aeeiiai? an? yeaeo?io?c?ieia?/i? aenia?eiaioe. O
?ic?iaoe? eiioeaioe?? aeine?aeaeaiue aeoeaio o/anoue i?eeiaee ni?aaaoi?e
ae?oeiaaieo ?ia?o.

Ai?iaaoe?y ?iaioe

Iniiai? iieiaeaiiy ?iaioe aoee i?aaenoaaeai? ia nai?ia?ao ?inoeoooo
o?c?ieia?? ?i. I. I. Aiaiiieueoey (Ee?a, 1996, 1997); I?aeia?iaeiiio
neiiic?oi? I?aeia?iaeiiai Oeaio?o Iieaeoey?ii? O?ceieia?? IAI Oe?a?ie
(Ee?a, 1997); I?aeia?iaeiiio eiia?an? Oiaa?enoaa Iae?iiaoe (Iiaee
I?eaai, NOA, 1997; EinAiaeaean, NOA, 1998); I?aeia?iaeiiio eiia?an?
A?io?ce/iiai Oiaa?enoaa (Eaican-n?o?, NOA, 1998).

IAOIAeEEA AeINE?AeAEAIUe

Ia’?eo aeine?aeaeaiue

Ni?iaeuei? aaiae??. A aenia?eiaioao aeei?enoiaoaaeenue ia?aeaioeo?eiaai?
iae?iie ni?iaeueieo aaiae??a uo??a o?ueio a?eiaeo a?oi: 1, 5-6 oa 14-15
aei?a iinoiaoaeueiiai ?icaeoeo. Aaiae?? iiaiia?iaeaeaieo uo??a
ia?iaeyeeny 0.1% ?ic/eiii i?iiace (Serva) o iiaeeo?eiaaiiio na?aaeiaeu?
?aea (DMEM, Sigma) ia i?ioyc? 7 oaeeei i?e 330N. Aeey a?eueo aei?ineeo
uo??a ia?iaea o?eaaea 15 oaeeei i?e iaci?iieo oaiia?aoo?? oa
eiioeaio?aoe?? oa?iaioo. Aaiae?? a?aeieaaee ia i?ioyc? 15-20 oaeeei oa
i?iaooaaee a na?aaeiaeu? DMEM, i?ney /iai ?cieueiaai? iae?iie
ia?aiineeeny a neeyiee Iao??. Ee?oeiia aaeaac?y aei aeia /aoee
caaa?ooaaeany i?ney 1-2 aiaeei ? iae?iie iiaee aooe aeei?enoai? a
aenia?eiaio?. Ia i?ioyc? aeine?aeaeaiue ee?oeie caeeoaeeny a na?aaeiaeu?
DMEM, a ci?ia ciai?oiueiai ?ic/eio i?iaiaeeeany ca aeiiiiiaith oaoi?ee
oaeaeei? eieaeueii? ia?ooc?? (Veselovsky et al., 1996) aaciina?aaeiuei a
iaeano? iae?iia ui aeine?aeaeo?oueny.

Iae?iie a?iieaiio. Iae?iie eoeueoeaoaaeeny ii iaoiaeeoe?, iienaii?
?ai?oa (Lux and Veselovsky, 1994). Ei?ioei, iae?iie a?iieaiio
iiaiia?iaeaeaieo uo??a e?i?? Wistar iaoai?/ii aeennioe?thaaeeny ?
ia?aiineeeny ia neeyiee Iao??, cacaeaeaa?aeue ia?iaeai? iie?i?ieo?iii.
U?euei?noue iinaaeee neeaaeaea 3000-10000/ni2. Eoeueoeaoaaiiy iae?ii?a
i?iaiaeeeiny a iiaeeo?eiaaiiio na?aaeiaeu? ?aea (DMEM, Sigma) c
aeiaeaiiyi 10% neai?ioee e?ia? ieiae?a ei?iae, 1% aetheice, 0.6 iI
aethoai?ia, 2.3 a/e NaHCO3, 6 ia/ie einoe?ia a NI2 ?ieoaaoi?? i?e 350N ?
5% NI2. Aenia?eiaioe i?iaiaeeeeny ia 12-17 aeaiue ae?iuoaaiiy iae?ii?a.

?ic/eie

?ic/eie aeey ciai?oiuei? ia?ooc?? i?noeee (a iI/e):

1) oei??ae oie?ia-150, KCl-5, CaCl2-1, MgCl2-1, HEPES-20, oao?iaeioienei
(TTX, Sigma) 0.5-1 (I, ?I aeiaiaeeany aei 7.4 aeiaeaiiyi Tris-OH.

2) NaCl-140, KCl-3, CaCl2-2, MgCl2-2, HEPES-20, OOO-0.25(I, D-AP5-20(M,
DNQX-20(M, ?I aeiaiaeeany aei 7.4 aeiaeaiiyi Tris-OH.

Aie?eaoe?y aeieaoi??a eae??aeo eaiae?a oao?aao?eaiii?y (OAA, Sigma) ?
4-ai?iii??eaeeia (4-AI, Aldrich) i?iaiaeeeany ca aeiiiiiaith oaoi?ee
oaeaeei? eieaeueii? ia?ooc?? (Veselovsky et al., 1996)

?ic/eie aeey aioo??oiueiee?oeiii? ia?ooc?? neeaaeaeeny (a iI/e):

1) KF-150, Tris-Cl-30, pH aeiaiaeeany aei 7.4 c aeiiiiiaith Tris-OH

2) KGlu-100, KCl-50, EGTA-5, MgCl2-5, pH aeiaiaeeany aei 7.4 c
aeiiiiiaith Tris-OH (Sigma).

Ciai?oiuei/aioo??oiueiee?oeii? ?ic/eie 1) aeei?enoiaoaaeeny i?e
aeine?aeaeaii? iioaioe?aeea?iaaieo eae??aeo no?oi?a, ?ic/eie 2) — i?e
aeine?aeaeaii? aaeuei?aii? neiaioe/ii? ia?aaea/e o iae?iiao a?iieaiio.

Aeaeo?io?c?ieia?/i? aei??thaaiiy

Aeine?aeaeaiiy eae??aeo no?oi?a niiaoe/ii? iaia?aie iae?ii?a ni?iaeueieo
aaiae??a i?iaiaeeeeny c aeei?enoaiiyi iaoiaeo iaeiiaeaeo?iaeii?
o?enaoe?? iioaioe?aeo c i?a?ea/aoei cai?ioiei ca’yceii c /anoioith
eiiooaoe?? a?ae 15 aei 25 eAoe (Brennecke and Lindemann, 1972). Aeaiee
iaoiae aeicaieya eiio?iethaaoe ??aaiue ?aaeueiiai iaia?aiiai
iioaioe?aeo, ui aeei?enoiaoaaeany a ?iaio? aeey ia/eneaiiy e?iaoe/ieo oa
noaoe?iia?ieo oa?aeoa?enoee eae??aeo no?oi?a. Ne?ae a?aecia/eoe, ui aei
ia?iaee i?eeiaeeny aeai?, a yeeo iaea?eueoa iiieeea a o?enaoe??
iioaioe?aeo i?e iaea?eueoeo aie?ooaeao eae??aiai no?oio neeaaeaea ia
a?eueo 5-10 iA.

Eae??aa i?ia?aei?noue iae?iiaeueii? iaia?aie ee?oei a?iieaiio
aeine?aeaeoaaeany c aeei?enoaiiyi iaoiaeeee o?enaoe?? iioaioe?aeo a
?aaeei? ?a?no?aoe?? a?ae oe?ei? ee?oeie. Eiiiainaoe?y ?ii?nieo no?oi?a ?
no?oio aeoieo aeeiioaaeany c aeei?enoaiiyi i?ioieieo ?/4 oa/aai
aiaeiaiai? eiiiainaoe?? a i?aeneethaa/?.

Aaeuei?ai? iinoneiaioe/i? no?oie (AINN) aeeeeeaeeny c aeei?enoaiiyi
iaoiaeeee eieaeueii? aeaeo?e/ii? noeioeyoe?? ciie neiaioe/iiai eiioaeoo
ei?ioeeie (3-5 in) ?iioeuenaie no?oio, ui i?iioneaany e??cue neeyio
i?e?ii?iaoeo c ciai?oi?i ae?aiao?ii e?i/eea aeecueei 1 iei, caiiaiaio
iicaee?oeiiei ?ic/eiii (Katz, 1969 — Liverpool University press;
Veselovsky and Grantyn, 1997). ?a?no?aoe?y AINN cae?enithaaeany ca
aeiiiiiaith iaoiaeo “patch-clamp” a eiio?ao?aoe?? ?a?no?aoe?? a?ae
oe?ei? ee?oeie.

A i?ioean? aenia?eiaioo aeai? aeene?aoecoaaeeny i?e /anoio? 5-10 eAoe ca
aeiiiiiaith aiaeiaiai-oeeo?iaeo ?ioa?oaen?a (Axon Instruments TL-1
interface) ? caa??aaeeny ia aei?noeiio aeeneo eiii’thoa?a c
aeei?enoaiiyi i?ia?aiiiai iaeaoo pClamp 6.0 (Axon Instruments, Foster
city, CA).

I?e?ii?iaoee aeoyaoaaeeny c ai?inee?eaoieo neeyieo eai?ey??a (Clark
Electromedical Instruments, UK). Ii?? i?e?ii?iaoie neeaaeaa 2-4 IIi.
Aenia?eiaioe i?iaiaeeeeny i?e oaiia?aoo?? 18-220N.

Ia?iaea ?acoeueoao?a aenia?eiaio?a

Aiae?c no?oi?a ? aeaieo i?iaiaeeany c aeei?enoaiiyi aiae?oe/ieo
i?ia?aiieo iaeao?a (pClamp 6.0, Axon Instruments; Origin 3.54, Microcol
Software; TIDA for Windows, HEKA elektronik). E?ea? eae??aeo no?oi?a
aoee ai?ieneiiaai? ca iiaeaeeth Oiaeaee?ia-Oaene?.

U?euei?noue no?oio aecia/aeany ye a?aeiioaiiy i?ae iaeneioiii
a?aeiia?aeiiai eaeeaaiai no?oio, aeeeeeaiiai ci?uaiiyi iioaioe?aeo aei
+40 iA, oa ?ii?noth niiaoe/ii? iaia?aie iae?iio. Aei??thaaiiy ?iiino?
iaia?ai aeeiioaaeeny ia/eneaiiyi ?eioaa?aeo i?ae e?eaith no?oio ca?yaea
iaia?aii? ?iiino?, aeeeeeaiiai a?ia?iiey??coth/ei ?iioeuenii aei -90 iA
a?ae i?aeo?eio?iiai iioaioe?aeo-60 iA.

Ie??i iiiaeaieo aeiaaee?a, an? aenia?eiaioaeuei? aeai? i?aaenoaaeai? a
aeae? na?aaei?o cia/aiue c? noaiaea?oiith iiieeeith. O-oano Nouethaeaioa
aeei?enoiaoaaany aeey ioe?iee noaoenoe/ii? aeinoia??iino? ?ica?aeiino?
i?ae aeaiia na?aaei?ie.

?ACOEUeOAOE AeINE?AeAEAIUe

Eae??aa i?ia?aei?noue niiaoe/ii? iaia?aie iae?ii?a ni?iaeueieo aaiae??a

?ioaa?aeueiee eaee?aee no?oi niiaoe/ii? iaia?aie ni?iaeuei?o aaiae??a
uo??a i?aeoe/ii a on?o aeine?aeaeaieo ee?oeiao i?a aooe iiae?eaiee ia
o?e ??cieo eiiiiiaioa, iacaeaaeii a?ae a?eo oaa?eie. Aeey ?icae?eaiiy
eae??aeo no?oi?a aoee aeei?enoai? i?ioieiee noeioeyoe??, a iiae?iaeoe?
iienai? ?ai?oa (Klee et al., 1995; Aaneeueaa, Oaaeoeiaa e Aanaeianeee,
1998; Fedulova et al., 1998). ?a?no?aoe?y i?iaiaeeeany c aeei?enoaiiyi
aioo??oiueiee?oeiiiai ?ic/eio KF/Tris-Cl, ui ia i?noeoue AAOA, aea c
aeinoaoiueith eiioeaio?aoe??th ?ii?a ooi?o (150 iI) aeey iiaiiai
aeieoaaiiy eaeueoe?e-caeaaeiiai eae??aiai no?oio (Kostyuk et al., 1975).
Ia ?en. 1-3 (A) iieacai? n?iaenoaa e?eaeo o?ueio oei?a eae??aeo no?oi?a,
ca?a?no?iaaieo a niiaoe/i?e iaia?ai? iae?ii?a ni?iaeueieo aaiae??a uo??a
a i?enooiino? TTX (1ieI).

Ia ?en. 1-3 (A, A) i?aaenoaaeai? e?iaoe/i? oa noaoe?iia?i?
oa?aeoa?enoeee o?ueio caaaeaieo oei?a eae??aeo no?oi?a a iae?iiao
ni?iaeueieo aaiae??a uo??a (a?aee?eo? neiaiee,(). Iino?ei? /ano
aeoeaaoe?? an?o o?ueio oei?a eae??aeo no?oi?a aei??thaaeeny oeyoii iieno
aeno?aeii? /anoeie e?eai? no?oi?a aeniioaioe?eiith ooieoe??th a
/aoaa?oiio nooiai?. Ai?ieneiaoe?y ?iaeoeaaoe?? o?aice?ioieo eae??aeo
no?oi?a i?iaiaeeeany c aeei?enoaiiyi iiiiaeniioaioe?eii? ooieoe?? aeey
oaeaeei-?iaeoeaoth/aainy no?oio (?en. 1A) oa aeaooaeniioaioe?eii?
ooieoe?? aeey iiaie?-?iaeoeaoth/aainy no?oio (a?ao?e oaeaeei? iino?eii?
/ano ?iaeoeaaoe?? ye ooieoe?? iaia?aiiiai iioaioe?aeo i?aaenoaaeaiee ia
?en. 2A).

?en. 1. E?iaoe/i? oa noaoe?iia?i? aeanoeaino? eae??aiai no?oio A-oeio o
iae?iiao ni?iaeueieo aaiae??a oa a?iieaiio. A. ?a?no?aoe?y
oaeaeei-?iaeoeaoth/aainy eae??aiai no?oio o iae?ii? ni?iaeueiiai
aaiae?y. A. Noaoe?iia?i? oa?aeoa?enoeee A-no?oio o iae?iiao ni?iaeueieo
aaiae??a (() oa a?iieaiio ((). A. Caeaaei?noue iino?eii? /ano
?iaeoeaaoe?? A-no?oio iae?ii?a ni?iaeuei?o aaiae??a (() oa a?iieaiio (()
a?ae ??aiy iaia?aiiiai iioaioe?aeo.

Aeai? caeaaeiino? noaoe?iia?ii? aeoeaaoe?? oa ?iaeoeaaoe?? a?ae aaee/eie
iaia?aiiiai iioaioe?aeo aeey oaeaeei-?iaeoeaoth/aainy (?en. 1A),
iiaie?-?iaeoeaoth/aainy (?en. 2A) oa ia?iaeoeaoth/aainy eae??aiai no?oio
cao?eiaiiai aei?yieaiiy (?en. 3A) i?aaenoaaeai? ia ?en. 1-3(A).
Aacia?a?aia e?i?y i?aaenoaaey? ai?ieneiaoe?th aeaieo ??aiyiiyi
Aieueoeiaia c ia?aiao?aie aeey aeoeaaoe?? ? ?iaeoeaaoe?? a?aeiia?aeii:
V1/2=-20 iA, k=11.8 iA; V1/2=-84 iA, k=-9.8 iA (?en. 1A); V1/2=-12.8 iA,
k=13.4 iA; V1/2=-54.6 iA, k=-12 iA (?en. 2A); V1/2= 15.3 mV, k= 12.5 mV
(?en. 3A).

?en. 2. E?iaoe/i? oa noaoe?iia?i? aeanoeaino? iiaie?-?iaeoeaoth/aainy
(IsK) eae??aiai no?oio o iae?iiao ni?iaeueieo aaiae??a oa a?iieaiio. A.
?a?no?aoe?y iiaie?-?iaeoeaoth/aainy eae??aiai no?oio o iae?ii?
ni?iaeueiiai aaiae?y. A. Noaoe?iia?i? oa?aeoa?enoeee
iiaie?-?iaeoeaoth/aainy no?oio o iae?iiao ni?iaeueieo aaiae??a (() oa
a?iieaiio ((). A. Caeaaei?noue “oaeaeei?” iino?eii? /ano ?iaeoeaaoe??
IsK no?oio iae?ii?a ni?iaeuei?o aaiae??a (() oa a?iieaiio (() a?ae
??aiy iaia?aiiiai iioaioe?aeo.

?en. 3. E?iaoe/i? oa noaoe?iia?i? aeanoeaino? ia?iaeoeaoth/aainy (IE)
eae??aiai no?oio o iae?iiao ni?iaeueieo aaiae??a oa a?iieaiio. A.
?a?no?aoe?y ia?iaeoeaoth/aainy eae??aiai no?oio o iae?ii? ni?iaeueiiai
aaiae?y. A. Noaoe?iia?i? oa?aeoa?enoeee IE no?oio o iae?iiao ni?iaeueieo
aaiae??a (() oa a?iieaiio ((). A. Caeaaei?noue iino?eii? /ano
aeo?aaoe?? IE no?oio iae?ii?a ni?iaeuei?o aaiae??a (() oa a?iieaiio (()
a?ae ??aiy iaia?aiiiai iioaioe?aeo.

Aeine?aeaeaiiy oa?iaeieia?/ii? /ooeeaino? iioaioe?aeea?aaieo eae??aeo
no?oi?a niiaoe/ii? iaia?aie iae?ii?a ni?iaeueieo aaiae??a aei aeieaoi??a
eae??aeo eaiae?a 4-AI ? OAA aeyaeei ??ciee nooi?iue oa?iaeieia?/ii?
/ooeeaino? caaaeaieo no?oi?a aei aeieaoi??a eae??aeo eaiae?a. Oae,
ciai?oiy aie?eaoe?y 2iI 4-AI i?ecaiaeeea aei aeieoaaiiy aie?ooaee
A-no?oio ia 80( 7% (n=8), a iiaie?-?iaeoeaoth/aainy no?oio ia 55 ( 6%
(n=8); ia?iaeoeaoth/eeny no?oi aoa ia /ooeeaee aei 4-AI. OAA a
eiioeaio?aoe?? 10 iI aeieoaaa iiaie?-?iaeoeaoth/eeny no?oi ia 40 ( 5%
(n=12), a E-no?oi ia 70 ( 5% (n=12) ? ia aeeeeeaa aaaiii? iiaeeo?eaoe??
aie?ooaee A-no?oio.

Eaiaee eaee?ai? i?ia?aeiino? o eoeueoeaiaaieo iae?iiao a?iieaiio

Aoee aeine?aeaeai? iioaioe?aeea?iaai? eaiaee eae??aiai no?oio o o?eaaei
eoeueoeaiaaieo (10-18 aei?a) iae?iiao a?iieaiio. Aeey ?icae?eaiiy
eae??aeo no?oi?a iae?ii?a a?iieaiio aoee canoiniaai? i?ioieiee
noeioeyoe?? aiaeia?/i? oei, ui aeei?enoiaoaaeeny aeey ?iciiae?eo
eae??aeo no?oi?a a naini?ieo iae?iiao. Ia ?en. 4A-A i?aaenoaaeai?
oaeaeei-?iaeoeaoth/eeny (A), iiaie?-?iaeoeaoth/eeny (A), a oaeiae
ia?iaeoeaoth/eeny eae??aee no?oi cao?eiaiiai aei?yieaiiy (A). Ia
anoaaeao aei a?aeiia?aeieo ?enoie?a i?aaenoaaeai? i?ioieiee noeioeyoe??,
ui aeei?enoiaoaaeeny aeey ?iciiae?eo ??cieo oei?a eae??aeo no?oi?a.

?en. 4. Iioaioe?aeea?iaai? eae??a? no?oie o eoeueoeaiaaieo iae?iiao
a?iieaiio. I?aaenoaaeai? oaeaeei-?iaeoeaoth/eeny (A),
iiaie?-?iaeoeaoth/eeny (A) oa ia?iaeoeaoth/eeny (A) eae??a? no?oie.

Aeoeaaoe?y iioaioe?aeea?iaaieo eae??aeo no?oi?a a iae?iiao a?iieaiio
caaeia?eueii iienoaaeany aeniioaioe?eiith ooieoe??th, caaaeaii? o
/aoaa?oee nooi?iue. Iioaioe?aeaea?aai? eae??a? no?oie ?noioiei ia?acii
a?ae??ciyeeny ca oaeaeeinooth ?oiuei? aeoeaaoe??, oi/a oey a?aei?ii?noue
aeae?eueea ciaiooaaeany i?e a?eueo iiceoeaieo cia/aiiyo iaia?aiiiai
iioaioe?aeo. Iino?ei? /ano aeoeaaoe?? aeey oaeaeei-, iiaie?- oa
ia?iaeoeaoth/aainy eae??aeo no?oi?a iiiioiiii ciaiooaaeeny i?e
ca?eueoaii? iaia?aiiiai iioaioe?aeo ? neeaaeaee a?aeiia?aeii 2 in, 12
in, 45 in i?e Vt=-10 iA, a oaeiae 1.5 in, 6 in ? 10 in i?e Vt=+50 iA.

?iaeoeaaoe?y oaeaeei-?iaeoeaoth/aainy no?oio ai?ieneioaaeanue iaei??th
aeniiiaioith (?en. 1A). Iino?eia /ano cia/ii ciaiooaaeany i?e
ca?eueoaii? aeaiiey??coth/aai ci?uaiiy iioaioe?aeo a?ae 37 in i?e -50 iA
aei 17 in i?e 50 iA (?en. 1A). A oie aea /an ?iaeoeaaoe?y
iiaie?-?iaeoeaoth/aainy eae??aiai no?oio iaee?auei /eiii iienoaaeany
noiith aeaio aeniiiaio. Iino?eia /ano iia?eueii? (oaeaeei?) aeniiiaioe
aa??thaaea a?ae 4500 in (550 in) i?e Vt=-20 iA aei 1800 in (300 in) i?e
Vt=+40 iA (?en. 2A).

Aeey aecia/aiiy aaee/eie noaoe?iia?ii? aeoeaaoe?? eae??aeo eaiae?a
aaee/eia i?ia?aeiino? aecia/aeany ye a?aeiioaiiy aie?ooaee no?oio i?ae
/an oanooth/aai ci?uaiiy iioaioe?aeo aei aeaeo?i?ooath/?? neee (Vm —
Ek), aea Ek — ??aiiaaaeiee iioaioe?ae aeey ?ii?a eae?th, Vm — aie?ooaea
oanooth/aai iioaioe?aeo. Aenia?eiaioaeuei? oi/ee aeey noaoe?iia?iiai
??aiy aeoeaaoe?? A-no?oio (?en. 1A, (), iiaie?-?iaeoeaoth/aainy
eae??aiai no?oio (?en. 2A, () oa no?oio cao?eiaiiai aei?yieaiiy (?en.
3A, () caaeia?eueii iienoaaeeny ??aiyiiyi Aieueoeiaia c ia?aiao?aie
V1/2=-22.1 iA, k=10. 8 iA (?en. 1A); V1/2=-4.5 iA, k=10. 6 iA (?en. 2A);
V1/2=18.5 iA, k=11. 5 iA (?en. 3A), aea V1/2 — iioaioe?ae iieiaeii?
aeoeaaoe??, k — eiao?oe??io e?ooecie. A?aeiia?aei? aeai? caeaaeiino?
??aiy noaoe?iia?ii? ?iaeoeaaoe?? a?ae aaee/eie iaia?aiiai iioaioe?aeo
aoee iienai? ??aiyiiyi Aieueoeiaia c ia?aiao?aie V1/2=-80.1 iA, k=-7.1
iA (?en. 1A); V1/2=-77.1 iA, k=-10. 4 iA (?en. 2A).

Iioaioe?aeea?iaai? eae??a? no?oie a o?eaaei eoeueoeaiaaieo iae?iiao
a?iieaiio aieiae?ee ??ciei nooiaiai oa?iaeieia?/ii? /ooeeaino? aei
aeieaoi??a eae??aeo eaiae?a 4-AI ? OAA. Ia ?en. 5 iieacaia ae?y aeaieo
aeieaoi??a eae??aeo eaiae?a ia ?ioaa?aeuei? eaee?a? no?oie (?en. 5A-A),
a oaeiae ia eae??aee no?oi A-oeio.

?en. 5. Oa?iaeieia?/i? aeanoeaino? iioaioe?aeea?iaaieo eae??aeo no?oi?a
o eoeueoeaiaaieo iae?iiao a?iieaiio. A. Aeieoth/ee aoaeo OAA (A) oa 4-AI
(A) ia ?ioaa?aeueiee eae??aee no?oi. A. Ae?y 4-AI ia eae??aee no?oi
A-oeio.

Oaeaeei-?iaeoeaoth/eeny eae??aee no?oi aoa ia /ooeeaee aei
iicaee?oeiiiai i?eeeaaeaiiy 10 iI OAA. A oie aea /an 4-AI a
eiioeaio?aoe?? 1iI aeieoaaa A-no?oi ia 20%, a a eiioeaio?aoe?? 5iI ia
75%. Iiaie?-?iaeoeaoth/eeny eae??aee no?oi aeieoaaany 10 iI OAA ia 55%.
Iicaee?oeiia i?eeeaaeaiiy 4-AI a eiioeaio?aoe?? 1iI i?ecaiaeeei aei
aeieoaaiiy iiaie?-?iaeoeaoth/aainy no?oio ia 45%, a a eiioeaio?aoe?? 5
iI ia 80%. Ia?iaeoeaoth/eeny eae??aee no?oi ia aieiae?a cia/ouith
oa?iaeieia?/iith /ooeea?noth aei 4-AI, i?ioa aeieoaaany OAA. Aeiaeaiiy a
iicaee?oeiiee ?ic/ei 10iI OAA i?ecaiaeeei aei ciaioaiiy aie?ooaea
oeueiai no?oio ia 70%.

Io?eiai? aenia?eiaioaeuei? aeai? ii aeine?aeaeaiith eae??ai?
i?ia?aeiino? a iae?iiao a?iieaiio ? ni?iaeueieo aaiae??a cacia/athoue,
ui iioaioe?aeea?iaai? eae??a? no?oie a iae?iiao a?iieaiio ca nai?ie
noaoe?iia?ieie, e?iaoe/ieie oa oa?iaeieia?/ieie aeanoeainoyie ia
a?ae??ciythoueny ?noioiei ia?acii a?ae a?aeiia?aeieo eae??aeo no?oi?a
naini?ieo iae?ii?a, iacaaaeth/e ia i?eiaeaaei?noue inoaii?o aei
ia?eoa??/ii? ia?aiai? nenoaie.

Ci?ie eae??ai? i?ia?aeiino? iae?ii?a ni?iaeueieo aaiae??a a ?aiiueiio
iinoiaoaeueiiio iioiaaiac?

Aeine?aeaeaiiy niaoeeo?/ieo ci?i a ?iciiae?e? iienaieo aeua oei?a
eae??aeo no?oi?a, ui a?aeaoaathoueny ai?iaeiaae aeaio ia?oeo oeaei?a
i?ney ia?iaeaeaiiy oaa?eie aoei c?iaeaia ?c canoinoaaiiyi
aenia?eiaioaeueieo i?aeoiae?a aeieeaaeii iienaieo ?ai?oa (Fedulova et
al., 1994). U?eueiino? eae??aeo no?oi?a aoee ci??yi? aeey o?ueio
a?eiaeo a?oi oaa?ei: 1, 5-6 oa 14-15 aei?a iinoiaoaeueiiai ?icaeoeo. A
eiaei?e a?oi? aoei aeine?aeaeaii ii 50 iae?ii?a.

Oaaeeoey 1.

A?eiaa

A?oia U?euei?noue no?oio, iA/iO

?ii?noue iaia?aie, iO Ieiua i?iaeoe?? niie, iei2

IfK IsK IK

?1 14.9( 8*** (55) 65.1( 28.5 (55) 23.2( 11.4 (55) 39.6( 11*** (55) 488(
154***

(55)

?5.. 6 25.9( 16.7 (50) 78.8( 34.8 (50) 17.7( 8.8

(50) 51( 13.5

(50) 689( 182***

(50)

?14.. 15 30.1( 23.9 (50) 75.6( 38.2

(47) 17.4( 11.9 (47) 55.3( 17.3

(50) 796( 261

(50)

I?ei?oee. Aeai? a oaaeeoe? i?aaenoaaeai? o aeae? na?aaei? cia/aiiy (
na?aaei? eaaae?aoe/ia a?aeoeeaiiy, a aeoaeeao cacia/aia e?euee?noue
aeine?aeaeaieo iae?ii?a. IfK — oa?aeei-?iaeoeaoth/eeny, IsK —
iiaie?-?iaeoeaoth/eeny, IK — ia?iaeoeaoth/eeny eae??a? no?oie.

An? o?e oeio no?oi?a aoee aeyaeai? i?aeoe/ii a eiaeiiio
aeine?aeaeoaaiiio iae?ii?, aea aie?ooaea no?oi?a aa??thaaea a cia/iiio
nooiai?. U?euei?noue an?o no?oi?a aei??thaaeany i?e ci?uaii? iaia?aiiiai
iioaioe?aeo aei +40 iA — a iaeano? iioaioe?ae?a, aea noaoe?iia?iee
??aaiue aeoeaaoe?? an?o no?oi?a aeinyaaa iaeneiaeueii? aaee/eie (?en.
1-3A). ?acoeueoao eiii’thoa?iiai aiae?co c aeei?enoaiiyi O-oanoa, ui aei
noaoenoe/ii? ??cieoe? u?eueiinoae ii eiaeiiio c o?ueio oei?a eae??aeo
no?oi?a aeey aeaio iine?aeiaieo a?eiaeo a?oi, iaaaaeaiee a Oaaeeoe? 1
(p>0. 95 *; p>0. 99 **).

Aeia?a a?aeiii, ui oi?ia iioaioe?aeo ae?? ci?ith?oueny a i?ioean?
ee?oeiiiai c?inoo ? aeeoa?aioe?thaaiiy ye a nii?, oae ? a iae??oao
ee?oeie (Spitzer and Lamborghini, 1976; Kullberg et al., 1977; Willard,
1980; Einothe, E?eooaeue, 1981). Caea?oueny oe?eeii i?aaii??iei
i?eiouaiiy, ui iiaeeo?eaoe?? eae??ai? i?ia?aeiino? a i?ioean? ee?oeiiiai
c?inoo ia eei?oiaai? iaeanoth niie ee?oeie. Oaeei /eiii, iiaeaeueoei
caaaeaiiyi aeine?aeaeaiiy aoei c’ynoaaiiy iaoai?cio aieeao iiaeeeaeo
iiaeeo?eaoe?e eae??ai? i?ia?aeiino? i?aneiaioe/ii? iaia?aie ia
aoaeoeai?noue neiaioe/ii? ia?aaea/? a iae?iiao a?iieaiio uo??a.

Niiioaii? oa aeeeeeaii? aaeuei?ai? iinoneiaioe/i? no?oie (AINN)

A ciai?oiueiio ?ic/ei?, ui i?no?oue OOO a iae?iiao, ui ciaoiaeyoueny a
?aaeei? o?enaoe?? iioaioe?aeo, niinoa??aaeeny niiioaii? AINN (nAINN).
Na?aaeiy aie?ooaea nAINN iaea e?i?eio caeaaei?noue a?ae i?aeo?eio?iiai
iioaioe?aeo ?c iioaioe?aeii ?aaa?n?? -18..-20 iA i?e aeaieo
iica/aioo??oiueiee?oeiii? eiioeaio?aoe?? ?ii?a oei?o. Ciai?oiy
aie?eaoe?y a?eeoeoe?ia a eiioeaio?aoe?? 5 (I i?ecaiaeeea aei iiaiiai oa
cai?ioiueiai aeieoaaiiy nAINN. Oe? no?oie aoee ?aeaioeo?eiaai? ye
GABA-?iaeoeiaai? aaeuei?ai? iinoneiaioe/i? Cl- — no?oie.

AINN iiaee aooe oaeiae aeeeeeai? oeyoii iicaee?oeiii? aeaeo?e/ii?
noeioeyoe?? ciie i?aneiaioe/iiai cae?i/aiiy ei?ioeeie (3-5 in)
aeaiiey??coth/eie ?iioeuenaie no?oio, ui i?iioneaany e??cue neeyiee
i?e?iaeaeo?iae, caiiaiaiee iicaee?oeiiei ?ic/eiii (?en. 6A). Aeeeeeai?
AINN (aAINN) aoee aiaeia?/i? nAINN ca e?iaoeeith aeoeaaoe?? ?
?iaeoeaaoe??. Aie?ooaea ona?aaeiaieo aAINN iaea e?i?eio caeaaei?noue
a?ae aaee/eie i?aeo??ioaaiiai iioaioe?aeo ?c iioaioe?aeii ?aaa?n??
i?eaeecii -20 iA (?en. 6A), ui a?aeiia?aea? iioaioe?aeo Ia?inoa aeey
aeaieo eiioeaio?aoe?e ?ii?a oei?o. Oaeei /eiii, aAINN aoee aecia/ai? ye
GABA-?iaeoeiaai? Cl— no?oie.

?en. 6. Noaoenoe/iee aiae?c aAINN ie?aieo neiaioe/ieo oa?i?iaeae
eoeueoeaiaaieo iae?ii?a a?iieaiio. A. ?a?no?aoe?y aAINN, iaaaaeai? 50
ia?oeo aAINN. A. Caeaaei?noue aiie?ooaee ona?aaeiaiieo aAINN a?ae ??aiy
i?aeo?eioaaiiai iioaioe?aeo. A. Ai?ieneiaoe?y aiieeooaeii? a?noia?aie
aAINN (?en. 6A) noiie iacaeaaeieo e?eaeo Aaona. A. Eaaioiaee aiae?c
aiieeooae aAINN (?en. 6A,A) i?iaaaeaiee ca iiaeaeeth Ioanniia ((). N —
/enei ?a?no?aoe?e, m — eaaioiaee ai?no.

?iciiae?e aiie?ooae aAINN

I?e noeioeyoe?? ie?aiiai neiaioe/iiai cae?i/aiiy aAINN cia/ii aa??thaaee
ii aie?ooae? a?ae 7-8 iA aei a?eueo i?ae 150 iA i?e i?aeo?eioaaiiio
iioaioe?ae? -75 iA. Aa??aoe?y aie?ooaee aAINN a 10 c 12 iae?ii?a iaea
aeia?a ae?aaeaiee aeene?aoiee oa?aeoa? (?en. 6A). Ai?ieneiaoe?y
aiie?ooaeiiai ?iciiae?eo aAINN noeoii?noth iacaeaaeieo e?eaeo Aaona
iieaco?, ui ?iciiae?e aie?ooae aAINN ia? aeene?aoiee oa?aeoa? c
aaee/eiith eaaioa 20 iA (?en. 6A). Aaee/eia eaaioa aa??thaaea o iaaeao
19-22 iA (na?aaeiy aaee/eia=20 iA, n=10) ? ia caeaaeeea a?ae aie?ooaee
iicaee?oeiiiai noeioeo. Aaee/eia i?aeo?eio?iiai iioaioe?aeo
iinoneiaioe/ii? ee?oeie a on?o aeiaaeeao neeaaeaea -75 iA.

Oaeei /eiii, io?eiai? aeai? aeacothoue ia oa, ui aeeeae iaae?aoi?o a
ie?aiiio neiaioe/iiio cae?i/aii? iae?ii?a a?iieaiio ia? eiia??i?niee
oa?aeoa?. Iaoai?ci aeeeaeo iaae?aoi?o ? eaaioiaei.

Eaaioiaee aiae?c aiie?ooaeiiai ?iciiae?eo aAINN a ?aieao iiaeae?
Ioanniia

Aia?oa caeii Ioanniia aoa canoiniaaiee i?e aeine?aeaeaii? iaoai?cio
neiaioe/ii? ia?aaea/? o ia?aiai-ioneoeueiiio niieo/aii? aeaae (Katz,
1969 — Liverpool University press). Ia nueiaiaeiyoi?e iiiaio caniae
eiia??i?niiai iieno i?ioean?a niiioaiiiai oa aeeeeeaiiai aea?eueiaiiy
iae?iiaae?aoi?o ? caaaeueiii?eeiyoeie.

?en. 7. Ii??aiyiiy eaaioiaiai ai?noo aeeeaeo iaae?aoi?o, ?ic?aoiaaiiiai
c aenia?eiaioo m= mean IPSC/mini oa ca iiaeaeeth Ioanniia m=ln(N/n0), N
— /enei ?a?no?aoe?e, n0 — /enei i?iione?a.

Aeey canoinoaaiiy caeiio Ioanniia aei iieno io?eiaieo aenia?eiaioaeueieo
aeaieo aeiaaa?oueny ia?aaanoe aacia?a?aiee aiie?ooaeiee ?iciiae?e aAINN
a aeene?aoiee. Ia ?en. 6A i?aaenoaaeai e?euee?niee ?iciiae?e eaaioia
aAINN aeey a?aeiia?aeiiai aiie?ooaeiiai ?iciiae?eo aAINN, iieacaiiai ia
?en. 6A. I?e iiaoaeia? aeene?aoiiai ?iciiae?eo ca iaeei eaaio i?eeiaeeny
aAINN c aie?ooaeith a iaaeao -8..-28 iA, ca aeaa eaaioa a?ae -28 iA
aei-48 iA. ?iciiae?e Ioanniia aeey a??ia?aeiino? aeeeaeo o eaaioia
iaae?aoi?o caieno?oueny a aeae? P (x)=e-mmx/x!, aea m — iaoaiaoe/ia
i/eeoaaiiy e?eueeino? eaaioia (eaaioiaee ai?no). Eaaioiaee ai?no
aecia/a?oueny ye a?aeiioaiiy noia?ii? e?eueeino? aeeeiooeo eaaio?a a
na??? c N aei?iaoaaiue aei e?eueeino? oeeo aei?iaoaaiue. sse aeaeii c
?en. 6A, aeene?aoiee ?iciiae?e aeeeaeo iaae?aoi?o aeinoaoiuei aeia?a
ei?aeth? c oai?aoe/ii ia/eneaiiei ca caeiiii Ioanniia (iieacaiee ().
Ei?aeyoe?y i?ae eaaioiaei ai?noii, ia/eneaiiei ii iaoiaeo “i?iione?a”
m=ln (N/n0), n0 — e?euee?noue i?iione?a, N — e?euee?noue aei?iaoaaiue, a
oaeiae cacia/aiiiai ye a?aeiioaiiy na?aaeiuei? aiie?ooaee
iinoneiaioe/iiai no?oio aei aie?ooaee iaeiiai eaaioa no?oio
m=meanIPSC/mini cacia/a? aeinoia??i?noue a?iioace i?i Ioanniiianueeee
oa?aeoa? i?ioeano (?en. 7).

Aieea iicaee?oeiii? eiioeaio?aoe?? ?ii?a eaeueoe?th ia aAINN

Aoa aeine?aeaeaiee aieea ciai?oiuei? eiioeaio?aoe?? ?ii?a eaeueoe?th ia
aaeuei?aio neiaioe/io ia?aaea/o a ie?aiiio neiaioe/iiio cae?i/aii?
eoeueoeaiaaieo iae?ii?a a?iieaiio. Aeia?a a?aeiii, ui i?ioean
aecioeeoica a i?aneiaioe/i?e iaia?ai? iiina?aaeeiaai aoiaeii ?ii?a
eaeueoe?th e??cue iaia?aio oa?i?iae? (Katz, 1969 — Liverpool University
press). Oaeiae aeia?a a?aeiii, ui ca?eueoaiiy iicaee?oeiii?
eiioeaio?aoe?? ?ii?a eaeueoe?th a iaaeao 0.. 5 iI i?ecaiaeeoue aei
ca?eueoaiiy aie?ooaee eaeueoe??aiai no?oio ye e??cue iecueeiii?iaiaee
oae ? aenieiii?iaiaee eiiiiiaio eaeueoe??aeo eaiae?a. Ioaea, ne?aeo?
i/?eoaaoe, ui ci?ia eiioeaio?aoe?? iicaee?oeiiiai eaeueoe?th aoaea
ci?ithaaoe eiia??i?noue aeeeaeo iaae?aoi?o. Ae?enii, a na??? c 10
aeine?ae?a aoei onoaiiaeaii, ui ca?eueoaiiy iicaee?oeiii? eiioeaio?aoe??
eaeueoe?th i?e o?eniaaieo ia?aiao?ao iicaee?oeiii? noeioeyoe??
i?ecaiaeeoue aei ca?eueoaiiy na?aaeiuei? aie?ooaee aAINN (?en. 8A).
Ca?eueoaiiy eiioeaio?aoe?? eaeueoe?th i?ecaiaeeei aei ca?eueoaiiy
eaaioiaiai ai?noo aeeeaeo iaae?aoi?o ? ia aieeaaei ia na?aaeith aaee/eio
iaeiiai eaaioa aAINN. Caeaaei?noue aie?ooaee aAINN a?ae iicaee?oeiii?
eiioeaio?aoe?? ?ii?a eaeueoe?th iaea neaii?aeaeueiee oa?aeoa? (?en. 8A).

?en. 8. Aieea ciai?oiueiee?oeiii? eiioeaio?aoe?? ?ii?a Na++ ia aAINN
ie?aieo neiaioe/ieo oa?i?iaeae iae?ii?a a?iieaiio. A. Cia?aaeai?
ona?aaeiai? aAINN, io?eiai? ia iaei?e ee?oei? i?e ??cieo eiioeaio?aoe?yo
?ii?a Na++. A. Caeaaei?noue aiie?ooaee aAINN a?ae ciai?oiueiee?oeiii?
eiioeaio?aoe?? ?ii?a Na++. Aeaii? i?aaenoaaeai? a aeae? mean ( SD.

Ca?eueoaiiy eaaioiaiai ai?noo aeeeaeo iae?iiaae?aoi?o a aaeuei?ai?e
neiaioe/i?e ia?aaea/? i?ae aie?aii aeieaoi??a eae??aeo eaiae?a

Aoa aea/aiee aieea i?e?iiey?ieo eiioeaio?aoe?e aeieaoi??a eae??aeo
eaiae?a ia neiaioe/io ia?aaea/o a ie?aiiio neiaioe/iiio cae?i/aii? a
oiiaao a?aenooiino? aaia?aoe?? iioaioe?aeo ae?? (a ?ic/ei?, ui i?noeoue
OOO). Ciai?oiy aie?eaoe?y 4-AI a eiioeaio?aoe?? 5iI i?ecaiaeeea aei
cai?ioiiai ca?eueoaiiy na?aaeiuei? aie?ooaee aAINN ia 90( 30% (?en. 9A,
n=7). Ca?eueoaiiy na?aaeiuei? aie?ooaee aAINN aoei iia’ycaia c
ca?eueoaiiyi eaaioiaiai ai?noo aeeeaeo iaae?aoi?o (anoaaeaiiy aei ?en.
9A) ? ia ci?ithaaei aaee/eie iaeiiai eaaioa. E?iaoeea niaaeo aAINN a
eiio?ie? oa i?enooiino? 4-AI ia ci?ithaaeany. Aie?eaoe?y 20iI OAA
i?ecaiaeeea aei cia/ii iaiueoiai aoaeoo, aie?ooaea aAINN c?inoaea ia
20( 5% (?en. 9A, n=5).

?en. 9. Ae?y aeieaoi??a iioaioe?aeea?iaaieo eae??aeo eaiae?a ia aAINN
ie?aieo neiaioe/ieo oa?i?iaeae iae?ii?a a?iieaiio. A. Cia?aaeai?
ona?aaeiai? aAINN a eiio?ie? oa i?e aie?eaoe?? 5iI 4-AI; ci?ia
eaaioiaiai ai?noo aeeeaeo iaae?aoi?o cia?aaeaia ia anoaaoe? e ?enoieo.
A. Ona?aaeiai? aAINN a eiio?ie? oa i?e aie?eaoe?? 20iI OAA.

Oaeei /eiii, aeieoaaiiy iioaioe?aeea?iaaieo eae??aeo eaiae?a
i?aneiaio/ii? iaia?aie i?ecaiaeeoue aei ca?eueoaiiy eaaioiaiai ai?noo
aeeeaeo iaae?aoi?o a ie?aiiio neiaioe/iiio cae?i/aii?.

IAAIAI?AIIss

Ii??aiyiiy aeanoeainoae a?aeiia?aeieo oei?a iioaioe?aeea?iaaieo eae??aeo
no?oi?a a iae?iiao a?iieaiio oa naini?ieo iae?iiao ia aeyaeei
noaoenoe/ii aeinoia??ieo a?aei?iiinoae a?eueoino? ?o noaoe?iia?ieo ?
e?iaoe/ieo ia?aiao??a. Eiia??ii, a?aeiia?aei? oeie aeine?aeaeaieo
eae??aeo no?oi?a naini?ieo oa oeaio?aeueieo iae?ii?a aecia/athoueny
aiaeia?/ieie (i?eiaeii? a cia/iiio nooiai? aiiieia?/ieie) oeiaie
eaiae?a. Oaea aiaeia?y iioe?aia a ia?aia?e nenoai?. Oae, e?iaoe/i? ?
oa?iaeieia?/i? aeanoeaino? iienaiiai a oe?e ?iaio? oaeaeeiai eae??aiai
no?oio A-oeio a cia/iiio nooiai? iiaiaeyoueny c aenia?eiaioaeueieie
aeaieie aeey aiaeia?/ieo A-eae??aeo no?oi?a, io?eiaieie ia aaaaoueio
?ioeo i?aia?aoao oeaio?aeueii? ia?aiai? nenoaie — iae?iiao oaeaiona
(Budde et al. 1992), iaiei?oeeaeueieo iae?iiao (Andreasen and Hablitz
1992) oa iaiiaoaeueieo naini?ieo iae?iiao (MacFarlane and Cooper 1991,
Fedulova et al. 1998). Nthaee iiaeia a?aeianoe oaeaeeo aeoeaaoe?th ?
?iaeoeaaoe?th c iino?eiith /ano ?iaeoeaaoe?? o iaaeao 15-30 in,
iioaioe?ae iieiaeii? ?iaeoeaaoe?? -85..-70 iA oa i?aeaeuaio /ooeea?noue
aei iicaee?oeiiiai i?eeeaaeaiiy 4-AI. Aeaye? a?aei?iiino? o ?iaioao
??cieo aaoi??a aeyaeythoueny a oa?aeoa?? caeaaeiino? iino?eii? /ano
?iaeoeaaoe?? eae??aiai no?oio A-oeio, ui iiaea aooe iia’ycaia ?c
iniaeeainoyie ooieoe?iiaeueieo aeanoeainoae eae??aeo eaiae?a A-no?oio a
oeaieiao ??cieo ae?eyiie ia?aiai? nenoaie. A iiceo nnaaoe?a aoee
?aeaioeo?eiaai? o?e oeio eae??aeo eaiae?a, ui a?aeiia?aeathoue ca
eae??aee no?oi A-oeio: Kv1. 4 (RCK4), Kv3. 4 (Raw3) oa Kv4. 2 (RK5, rat
shall: Baldwin et al., 1991; Rettig et al., 1992; Stuhmer et al., 1989).
I/aaeaeii, ui Kv3. 4 eaiae ia iiaea aecia/aoe aeine?aeaeaiee oei no?oio,
ai Kv3. 4 eaiae, io?eiaiee caniaii aeni?an?? a Xenopus oocytes, aieiae??
i?aeaeuaiith /ooeea?noth aei TAA (ID50=0.3 mM: Rettig et al., 1992). C
?ioiai aieo, Kv1. 4 oa Kv4. 2 eaiaee a?aeiia?aei? ca eae??a? no?oie, a
cia/iiio nooiai? noiae? c oaeaeeei eae??aei no?oiii ii nai?e /ooeeaino?
aei 4-AI oa a?aeiinii? ?acenoeaiino? aei OAA. ?ioiioeeoio?i?/i?
aeine?aeaeaiiy, i?iaaaeai? a ??cieo ae?eyieao aieiaiiai iiceo, iieacaee,
ui eaiae Kv4. 2 ciaoiaeeoueny a iniiaiiio a iaeano? niie ? aeaiae?eoiiai
aea?aaa iae?iia, a oie /an ye Kv1. 4 cina?aaeaeaiee a aenii? oa ia?aiaeo
oa?i?iaeyo (Tsaur et al., 1992; Cooper et al., 1998; iaeiae
Martunez-Padryn and Ferrus, 1997). E??i oiai, oaeaee?noue aeoiaeo c
?iaeoeaaoe?? aeine?aeaeaiiai A-oeio eae??aiai no?oio (iino?eia /ano 45
in) a?eueo a?aeiia?aea? oaeaeeino? aeoiaeo c ?iaeoeaaoe?? Kv4. 2 eaiaeo,
a oie /an ye Kv1. 4 eaiae ia? ?noioii iaiueoo oaeaee?noue aeoiaeo c
?iaeoeaaoe??. Oiio, iaea?eueo ae?ia?aeii, ui aeine?aeaeaiiee oei
eae??ai? i?ia?aeiino? a?aeiia?aea? Kv4. 2 oeio eae??aiai eaiaeo.

Iiaie?-?iaeoeaoth/eeny eae??aee no?oi aeoeao?oueny a aeae?eueea ?ac
iia?euei?oa A-no?oio. ?iaeoeaaoe?y iienoaaeany aeaooaeniioaioe?eiith
ooieoe??th c iino?eieie /ano aeae?eueea nioai oa oeny/ i?e?naeoiae
a?aeiia?aeii. Iiaeia aoei a i?eionoeoe, ui iiaie?-?iaeoeaoth/eeny
eae??aee no?oi aecia/a?oueny aeaiia oeiaie eae??aeo eaiae?a. Iaeiae,
noaoenoe/ii aeinoia??ieo a?aei?iiinoae o e?iaoe/ieo ? oa?iaeieia?/ieo
ia?aiao?ao aeaio aeuacacia/aieo eiiiiiaio?a no?oio aeyaeaia ia aoei.
E??i oiai aoei iieacaii, ui iiaie?-?iaeoeaoth/eeny eae??aee no?oi
(RBK1), ii nai?i ia?aiao?ai aiaeia?/iee iienaiiio aeua eae??aiio no?oio,
oaeiae oa?aeoa?eco?oueny aeaooaeniioaioe?eiei oiaeii ?iaeoeaaoe?? c
iino?eieie /ano ii?yaeeo 50-100 in oa 5-10 n a?aeiia?aeii (Christie et
al., 1989).

Ii??a aeoeaaoe?? eae??aiai no?oio E-oeio eaaeeoue a iaaeao -20 iA,
iioaioe?ae iieiaeii? aeoeaaoe?? neeaaea? +15 iA. E-no?oi aeoeao?oueny
iiaie? c iino?eii? /ano aeanyoee i?e?naeoiae ? ia ?iaeoeao?oueny
i?eiaeii? ai?iaeiaae 10-15 n i?e iino?eiiio ??ai? aeaiiey?ecaoe??
iaia?aie. Ia?iaeoeaoth/eeny eae??aee no?oi ia aoa /ooeeaee aei 4-AI,
iaeiae aeieoaaany 10iI OAA ia 70-80%. Aeine?aeaeaiiy a iaeano?
iieaeoey?ii? a?ieia?? (Stuhmer et al., 1989) aeyaeee o?e oeio aai?a, ui
a?aeiia?aeathoue ca eae??a? eaiaee cao?eiaiiai aei?yieaiiy c
aeanoeainoyie, aeecueeeie aei aeanoeainoae aeine?aeaeaiiiai no?oio: Kv1.
2 (RCK2), Kv1. 1 (RCK1) oa Kv1. 5 (RCK5). Oe? eaiaee aieiae?thoue
noiaeeie e?iaoe/ieie ia?aiao?aie, aea a?ae??ciythoueny ca
oa?iaeieia?/iith /ooeeaino? aei OAA. IC50 aeey RCK1, RCK2 ? RCK5 eaiae?a
neeaaea? a?aeiia?aeii 0.6, 7 oa 129 iI. Oiio, aeine?aeaeaii?e eae??aee
no?oi cao?eiaiiai aei?yieaiiy, iaea?eueo iaaii, aecia/a?oueny Kv1. 2
oeiii eae??aiai eaiaeo.

Aeine?aeaeaiiy iiaeeo?eaoe?e eae??ai? i?ia?aeiino? niiaoe/ii? iaia?aie
naini?ieo iae?ii?a iieacaee, ui na?aaeiy u?euei?noue oaeaeei- ?
iiaie?-?iaeoeaoth/eony no?oi?a ca?eueooth?oueny ai?iaeiaae ia?oeo i’yoeo
aei?a iinoiaoaeueiiai ?icaeoeo ? ia ci?ith?oueny a ianooii? aeanyoue
aei?a. Na?aaeiy u?euei?noue ia?iaeoeaoth/aainy eae??aiai no?oio
ciaioo?oueny a ia?oee ? ia ci?ith?oueny a ae?oaee aeine?aeaeaiee ia??iae
?aiiueiai iiniaoaeueiiai ?icaeoeo. I?e oeueiio, e?euee?noue iae?ii?a, ui
iathoue u?euei?noue oaeaeei-?iaeoeaoth/aainy eae??aiai no?oio a?eueo 20
?A/?O, ca?eueoo?oueny a i?ioean? iioiaaiaco. Oea icia/a?, ui cia/aiiy
oaeaeei-?iaeoeaoth/aainy eae??aiai no?oio a ?aaoeyoe?? caoaeeeaino?
iae?iia c?inoa? c ca?eueoaiiyi a?eo oaa?eie. A oie aea /an, e?euee?noue
iae?ii?a, ui iathoue u?euei?noue ia?iaeoeaoth/aainy eae??aiai no?oio
a?eueoa 25 ?A/?O, ciaioo?oueny ai?iaeiaae ?aiiueiai iioiaaiaco.
Aeine?aeaeaiiy ?yaeo aaoi??a ii eae??a?e i?ia?aeiino? oeaio?aeueieo
iae?ii?a, a oiio /ene? ? iae?ii?a a?iieaiio (Bader et al., 1985; Aguayo,
1989; Surmier et al., 1991; Wu and Barish, 1994; Klee et. al, 1995) ia
?aii?o aoaiao iioiaaiaoe/iiai ?icaeoeo aeacothoue ia aeayeo aiaeia?th a
i?ioeanao ci?i u?eueiino? eae??aeo no?oi?a a iae?iiao ni?iaeueieo
aaiae??a oa iae?iiao a?iieaiio. Oae, u?euei?noue iiaie?-?iaeoeaoth/aainy
eae??aiai no?oio a iae?iiao NA1 ? CA3 iaeano? a?iieaiio uo??a
ca?eueoo?oueny i?ioyaii ia?oeo aeaio oeaei?a iinoiaoaeueiiai ?icaeoeo.
Aiaeia?/i? iiaeeo?eaoe?? niinoa??aaeeny ? a iaoeo aeine?aeaeaiiyo
eae??aeo no?oi?a iae?ii?a ni?iaeueieo aaiae??a. Iiaeeeai, oea yaeua ?
/anoeiith o?c?ieia?/iiai iaoai?cio, ui ? ni?eueiei aeey aaaaoueio oei?a
iae?iiaeueieo ee?oei. I/aaeaeii, ui ci?ia u?eueiino? eae??aeo eaiae?a
i?ecaiaeeoue aei iiaeeo?eaoe?? oi?ie oa o?eaaeino? iioaioe?aeo ae??, ui
a naith /a?ao oyaia ca niaith aa??aoe?th a e?eueeino? eaeueoe?th, ui
i?iieea? ana?aaeeio ee?oeie i?ae /an i?ioiaeaeaiiy iioaioe?aeo ae??.
Iniaeeao ?ieue a oeueiio a?ae?a?athoue eae??a? eaiaee, ?icoaoiaai?
aaciina?aaeiuei a iaeano? i?aneiaioe/iiai cae?i/aiiy iae?iia. Ci?ia
oi?ie iioaioe?aeo ae?? a oe?e iaeano? ? a?aeiia?aeia ci?ia e?eueeino?
i?iieeath/aai ana?aaeeio eaeueoe?th iiaeooue aaciina?aaeiuei aieeaaoe
ia i?aneiaioe/iee iaoai?ci aeeeaeo iaae?aoi?o.

Aeine?aeaeaiiy ?yaeo aaoi??a aeacothoue, ui eae??a? eaiaee
i?aneiaioe/iiai cae?i/aiiy iae?iia iiaeooue aooe a cia/i?e i???
aiiieia?/i? eae??aei eaiaeai niiaoe/ii? iaia?aie (Martunez-Padryn and
Ferrus, 1997; Cooper et al., 1998). Caea?oueny i?aaii??iei i?eiouaiiy
i?i oa, ui ci?ie eae??ai? i?ia?aeiino? niie iae?iia iiaeooue a yeiio-oi
nooiai? (i?eiaeii? ye?nii) a?aeaeaaoe a?aeiia?aei? ci?ie i?ia?aeiino?
an??? iae?iiaeueii? iaia?aie. Aeine?aeaeaiiy ae?? aeieaoi??a
iioaioe?aeea?iaaieo eae??aeo eaiae?a (OAA, 20iI ? 4-AI, 5 iI) ia
neiaioe/io ia?aaea/o iae?ii?a a?iieaiio iieacaee, ui aeieoaaiiy eae??aeo
eaiae?a i?aneiaioe/ii? iaia?aie i?ecaiaeeoue aei ca?eueoaiiy ?iia??iino?
aeeeaeo iaae?aoi?o a ie?aiiio neiaioe/iiio cae?i/aii?. Aoaeo iiaea aooe
iiyniaiee ne?aeoth/ei /eiii. Aeieoaaiiy eae??aeo eaiae?a i?ecaiaeeoue
aei ca?eueoaiiy aaee/eie oa o?eaaeino? aeaiiey??caoe?? i?aneiaioe/ii?
iaia?aie, ui ca?eueoo? aaee/eio eaeueoe??aiai no?oio e??cue
iioaioe?aeea?iaai? eaeueoe??a? eaiaee. A naith /a?ao, ca?eueoaiiy
e?eueeino? eaeueoe?th, ui i?iieea? ana?aaeeio i?aneiaioe/ii? oa?i?iae?
ci?ith? ?iia??i?noue aeeeaeo iaae?aoi?o. ?ai?o aoei iieacaii, ui eae??a?
no?oie IfK, IsK oa IK — oei?a naini?ieo ? oeaio?aeueieo iae?ii?a
aieiae?thoue ??ciei nooiaiai /ooeeaino? aei OAA ? 4-AI (McFarlane and
Cooper, 1991; Klee et al., 1995; Fedulova et al., 1998). No?oi IfK
iaea?eueo /ooeeaee aei 4-AI ? ia /ooeeaee aei OAA, a oie /an ye eae??a?
no?oie IsK ? IK a cia/iiio nooiai? aeieothoueny i?e?iiey?ieie
eiioeaio?aoe?yie OAA. A iaoeo aenia?eiaioao aie?eaoe?y 5 iI 4-AI
i?ecaiaeeea aei ca?eueoaiiy aie?ooaee aAINN a na?aaeiueiio ia 90%, a oie
/an ye OAA 20iI aeeeeeaa ca?eueoaiiy aaee/eie aAINN a na?aaeiueiio ia
20%. Oeae oaeo iiaea aeacoaaoe ia aeii?ioth/o ?ieue eae??aiai no?oio IfK
(A-oeio) a oi?ioaaii? eae??ai? i?ia?aeiino? i?aneiaioe/ii? iaia?aie
aeine?aeaeoaaiiai oeio iae?ii?a.

AENIIAEE

1. Aiae?c eae??ai? i?ia?aeiino? niiaoe/ii? iaia?aie iae?ii?a ni?iaeueieo
aaiae??a ? a?iieaiio iieaco? iayai?noue i?eiaeii? o?ueio oei?a
iioaioe?aeea?iaaieo eae??aeo no?oi?a a aeine?aeaeaieo oeiao ee?oei.
Nthaee iiaeia a?aeianoe oaeaeei-?iaeoeaoth/eeny, iiaie?-?iaeoeaoth/eeny
oa ia?iaeoeaoth/eeny eae??a? no?oie. Eae??a? no?oie iae?ii?a ni?iaeueieo
aaiae??a ii nai?i noaoe?iia?iei, e?iaoe/iei oa oa?iaeieia?/iei
ia?aiao?ai ia a?ae??ciythoueny nooo?aei ia?acii a?ae a?aeiia?aeieo oei?a
eae??aeo no?oi?a iae?ii?a a?iieaiio.

2. U?euei?noue eae??aeo no?oi?a IfK ? IsK niiaoe/ii? iaia?aie iae?ii?a
ni?iaeueieo aaiae??a noaoenoe/ii aeinoia??ii ca?eueoo?oueny i?ioyaii
ia?oeo aeaio oeaei?a iinoiaoaeueiiai ia??iaeo, a oie /an ye u?euei?noue
IK -no?oio ciaioo?oueny ia oiio ae ?ioa?aae?.

3. Aeieaoi?e iioaioe?aeea?iaaieo eae??aeo eaiae?a 4-AI ? OAA
aeeeeeathoue ca?eueoaiiy na?aaeiuei? aie?ooaee aAINN GABAA ?aoeaioi??a
neiaioe/ii? oa?i?iae? iae?ii?a a?iieaiio, i?e oeueiio 4-AI (5iI)
aeeeeea? cia/ii a?eueoee aoaeo (90( 30%) a ii??aiyii? c 20iI OYA (20(
5%). Ca?eueoaiiy aie?ooaee aAINN oaeiae iiaei aooe io?eiaia oeyoii
ca?eueoaiiy iicaee?oeiii? eiioeaio?aoe?? ?ii?a eaeueoe?th.

4. Eaaioiaee aiae?c aaeuei?aii? neiaioe/ii? ia?aaea/? eoeueoeaiaaieo
iae?ii?a a?iieaiio ia ??ai? ie?aii? neiaioe/ii? oa?i?iae? a aeaieo
aenia?eiaioaeueieo oiiaao iieaco? aaeaeaaoi?noue canoinoaaiiy iiaeae?
Eaooea aeey iieno ioeueoeaac?eoey?iiai aeeeaeo iaae?aoi?o a aaeuei?aieo
neiainao a?iieaiio nnaaoe?a.

5. Ca?eueoaiiy na?aaeiuei? aie?ooaee aAINN ie?aii? neiaioe/ii? oa?i?iae?
i?ae aieeaii aeieaoi??a eae??aeo eaiae?a iiynith?oueny ca ?aooiie
ca?eueoaiiy eaaioiaiai ai?noo aeeeaeo iaae?aoi?o i?e iaci?i?e aiie?ooae?
eaaioa aAINN.

Ii io?eiaiei aeaiei aoei iioae?eiaaii oae? i?aoe?:

1. Ae. A. Aaneeueaa, I. N. Aanaeianeee e N. A. Oaaeoeiaa.
Iioaioeeae-aeoeae?oaiua eaeeaaue oiee niiaoe/aneie iaia?aiu naini?iuo
iae?iiia e?un a ?aiiai iinoiaoaeueiii ia?eiaea. Iae?ioeceieiaey, 1998.
— o. 30. — no?. 25-35.

3. Ae. A. Aaneeueaa., A. A. Enaaaa, N. A. Oaaeoeiaa e I. N.
Aanaeianeee. I?aneiaioe/aneay ?aaoeyoeey oi?iiciie neiaioe/aneie
ia?aaea/e iae?iiia aeiiieaiia e?un aeieaoi?aie eaeeaauo eaiaeia.
Iae?ioeceieiaey, 1998.-o.30.-no?. 336-340.

2. S. A. Fedulova, D. V. Vasilyev and N. S. Veselovsky Voltage-operated
potassium currents in the somatic membrane of rat dorsal root ganglion
neurons: ontogenetic aspects. Neuroscience, 1998. -v.85. — p.497-508.

Oace aeiiia?aeae:

1. S. A. Fedulova, D. Owen, D. V. Vasilyev and N. S. Veselovsky.
Developmental study of the expression of potassium channels in the
somatic membrane of sensory neurons. Society for Neuroscience 27th
Annual Meeting, 1997. Abstract Book, 681.4

2. D. V. Vasilyev, S. A. Fedulova, E. V. Isaeva and N. S. Veselovsky.
Fast-Inactivating potassium current in cultured rat hippocampal neurons.
International Workshop “Intracellular signalling” in association with
XXXIII International Congress of Physiological Sciences, 1997, June
26-28, Kiev. Neurophysiology, 1997.-v.29.- p.376.

3. D. V. Vasilyev, S. A. Fedulova, E. V. Isaeva and N. S. Veselovsky.
Three distinct types of potassium current in cultured rat hippocampal
neurons. Biophysical Society 1998 Annual Meeting. Abstract Book,
05C-05D.

4. S. A. Fedulova, D. V. Vasilyev, E. V. Isaeva, M. E. Barish and N. S.
Veselovsky. Multiple potassium channels regulate neurotransmitter
release from single boutons of inhibitory hippocampal synapses in
culture. Society for Neuroscience 28th Annual Meeting, 1998.

5. D.V. Vasilyev, S.A. Fedulova, E.V. Isaeva, D.S. Faber and N.S.
Veselovsky. Effect of different concentration of extracellular Ca2+ on
IPSC evoked at single synapse of cultured hippocampal neurons. Society
for Neuroscience 28th Annual Meeting, 1998.

Iaaaaeaia aeena?oaoe?y aeeeaaeaia ia 98 noi??ieao, aeeth/ath/e nienie
e?oa?aoo?e (149 aeaea?ae), aeeth/a? a naaa anooi, iaeyae e?oa?aoo?e,
iaoiaeeeo, ?acoeueoaoe aeine?aeaeaiue, iaaiai?aiiy oa aeniiaee. O ?iaio?
aeei?enoaii 12 ?ethno?aoe?e.

Aiioaoe??:

Aaneeue?a Ae. A. Iioaioe?aeaeoeaiaai? eae??a? no?oie iae?ii?a
ni?iaeueieo aaiae??a oa a?iieaiio uo??a: iioiaaiac oa ?ieue o
aaeuei?ai?e neiaioe/i?e ia?aaea/?. — ?oeiien.

Aeena?oaoe?y ia caeiaoooy a/aiiai nooiaiy eaiaeeaeaoa a?ieia?/ieo iaoe
ca niaoe?aeueiinoth 03.00.02 — A?io?ceea. — ?inoeooo O?c?ieia?? ?i. I.
I. Aiaiiieueoey, Ee?a, 1998.

Aeena?oaoe?y i?enay/aia aea/aiith aeanoeainoae iioaioe?aeea?iaaieo
eae??aeo no?oi?a iae?iiaeueieo iaia?ai ni?iaeueieo aaiae??a oa a?iieaiio
uo??a i?ae /an ?aiiueiai iinoiaoaeueiiai ?icaeoeo. ?acoeueoaoe
i?iaaaeaieo aeine?aeaeaiue iieacaee, ui iioaioe?aeea?iaai? eae??a?
no?oie A -, DR — oa E — oeio niiaoe/ii? iaia?aie iae?ii?a ni?iaeueieo
aaiae??a ca nai?ie e?iaoe/ieie, noaoe?iia?ieie oa oa?iaeieia?/ieie
ia?aiao?aie ia a?ae??ciythoueny nooo?aei ia?acii a?ae a?aeiia?aeieo
eae??aeo no?oi?a iae?ii?a a?iieaiio. Anoaiiaeaii, ui na?aaei? u?eueiino?
A — ? DR-no?oi?a niiaoe/ii? iaia?aie iae?ii?a ni?iaeueieo aaiae??a
ca?eueoothoueny ai?iaeiaae ia?oeo i’yoeo aei?a iinoiaoaeueiiai ?icaeoeo,
a oie /an ye u?euei?noue E-no?oio ciaioo?oueny ca oie aea ia??iae, ? ia
ci?iththoueny o ianooii? aeanyoue aei?a. Iieacaii, ui a oiiaao
a?aenooiino? iioaioe?aeo ae?? (a ?ic/ei?, ui i?noeoue OOO) ci?ia
eae??ai? i?ia?aeiino? iaia?aie aaeuei?aii? neiaioe/ii? oa?i?iae? (i?ae
aieeaii oao?aao?eaiii?th aai 4-ai?iii??eaeeio) i?ecaiaeeoue aei
ca?eueoaiiy na?aaeiuei? aie?ooaee iinoneiaioe/ii? a?aeiia?ae? i?e
iaci?iieo ia?aiao?ao ciai?oiueiee?oeiii? noeioeyoe??. I?iaaaeaiee
eaaioiaee aiae?c iieacaa, ui ci?ia iinoneiaioe/ii? a?aeiia?ae? i?ae
aieeaii aeieaoi??a eae??aeo eaiae?a a?aeaoaa?oueny ca ?aooiie
ca?eueoaiiy eaaioiaiai ai?noo aeeeaeo iaae?aoi?o c ie?aii? neiaioe/ii?
oa?i?iae? i?e iaci?ii?e aaee/ei? iaeiiai eaaioa.

Eeth/ia? neiaa: eae??a? eaiaee, iioiaaiac, neiaioe/ia ia?aaea/a,
eaaioiaee aiae?c.

Aaneeueaa Ae. A. Iioaioeeaeaeoeae?oaiua eaeeaaua oiee iae?iiia
nieiaeueiuo aaiaeeaa e aeiiieaiia e?un: iioiaaiac e ?ieue a oi?iiciie
neiaioe/aneie ia?aaea/a. — ?oeiienue.

Aeenna?oaoeey ia nieneaiea o/aiie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe
ii niaoeeaeueiinoe 03.00.02 — Aeioeceea. — Einoeooo Oeceieiaee
ei. A. A. Aiaiiieueoea, Eeaa, 1998.

Aeenna?oaoeey iinayuaia eco/aieth naienoa iioaioeeaeoi?aaeyaiuo eaeeaauo
oieia iae?iiaeueiuo iaia?ai nieiaeueiuo aaiaeeaa e aeiiieaiia e?un a
i?ioeanna ?aiiaai iinoiaoaeueiiai ?acaeoey.

A ianoiyuae ?aaioa auee enneaaeiaaiu o?e oeia iioaioeeaeoi?aaeyaiuo
eaeeaauo oieia iae?iiia nieiaeueiuo aaiaeeaa e aeiiieaiia, ii?aaeaeaiu
eo noaoeeiia?iua, eeiaoe/aneea e oa?iaeieiae/aneea oa?aeoa?enoeee, a oae
aea eciaiaiey ieioiinoe oieia a ?aiiai iinoiaoaeueiii ia?eiaea. Aieaa
oiai, auee enneaaeiaaiu aeeyiey eciaiaiee eaeeaaie i?iaiaeeiinoe (i?e
iiiiue aeieaoi?ia eaeeaauo eaiaeia) i?aneiaioe/aneie iaia?aiu ia
naienoaa neiaioe/aneie ia?aaea/e eoeueoeae?oaiuo iae?iiia aeiiieaiia.

N?aaiaiea naienoa niioaaonoaothueo oeiia iioaioeeaeoi?aaeyaiuo eaeeaauo
oieia a iae?iiao aeiiieaiia e naini?iuo iae?iiao ia auyaeei
noaoenoe/anee aeinoiaa?iuo ?acee/ee aieueoeinoaa eo noaoeeiia?iuo e
eeiaoe/aneeo ia?aiao?ia. Ii-aeaeeiiio, niioaaonoaothuea oeiu eaeeaauo
oieia enneaaeiaaiiuo naini?iuo e oeaio?aeueiuo iae?iiia ii?aaeaeythony
aiaeiae/iuie (eee ii e?aeiae ia?a a cia/eoaeueiie noaiaie aiiieiae/iuie)
oeiaie iaeeii/iuo eaiaeia.

A iicaa ieaeiieoathueo auee eaeaioeoeoee?iaaiu o?e oeia eaeeaauo eaiaea,
i?iaeooee?othuea eaeeaaue oie, niiinoaaeiue ii naiei eeiaoe/aneei
ia?aiao?ai n enneaaeiaaiiui a ianoiyuae ?aaioa eaeeaaui oieii A-oeia:
Kv1.4 (RCK4), Kv3.4 (Raw3) e Kv4.2 (RK5, rat shall: Baldwin et al.,
1991; Rettig et al., 1992; Stuhmer et al., 1989). I/aaeaeii, /oi Kv3.4
eaiae ia iiaeao ii?aaeaeyoue enneaaeiaaiiue oei oiea, oae eae Kv3.4
eaiae, iieo/aiiue iaoiaeii yeni?annee a Xenopus oocytes, iaeaaeaao
iiauoaiiie /oanoaeoaeueiinoueth e TYA (ID50 = 0.3 mM: Rettig et al.,
1992). N ae?oaie noi?iiu, Kv1.4 e Kv4.2 eaiaeu i?iaeooee?otho eaeeaaua
oiee, a cia/eoaeueiie noaiaie noiaeiua n auno?ui eaeeaaui oieii ii naiae
/oanoaeoaeueiinoe e 4-AI e ioiineoaeueiie ?acenoeaiinoe e OYA.
Eiioiioeeoioeie/aneea enneaaeiaaiey, i?iaaaeaiiua a ?acee/iuo o/anoeao
aieiaiiai iicaa, iieacaee, /oi eaiae Kv4.2 eieaeecoaony a iniiaiii a
iaeanoe niiu e aeaiae?eoiiai aea?aaa iae?iia, a oi a?aiy eae Kv1.4
nin?aaeioi/ai a aeniia e ia?aiuo oa?ieiaeyo (Tsaur et al., 1992; Cooper
et al., 1998), iaeiaei ni. Martunez-Padryn and Ferrus, 1997. Iiyoiio,
iaeaieaa aa?iyoii, /oi eaeaioeoeoee?iaaiiue oei eaeeaaie i?iaiaeeiinoe
niioaaonoaoao Kv4.2 oeio eaeeaaiai eaiaea.

Eaeeaaue oie DR-oeia aeoeae?oaony a ianeieueei ?ac iaaeeaiia A-oiea;
iioaioeeae iieiaeiiie aeoeaaoeee (V1/2) DR-oiea, naeaeioo ioiineoaeueii
V1/2 A-oiea ia 10iA a iaeanoue aieaa iieiaeeoaeueiuo iioaioeeaeia.
A?aiaiiay eiaeoeaaoeey DR-oiea iienuaaeanue aeaooyeniiiaioeeaeueiie
ooieoeeae n iinoiyiiuie a?aiaie ianeieueei nioai e ouny/ ieeeenaeoiae
niioaaonoaaiii. Iiaeii auei au i?aaeiieiaeeoue, /oi
iaaeeaiii-eiaeoeae?othueeny eaeeaaue oie ii?aaeaeyaony aeaoiy oeiaie
eaeeaauo eaiaeia. Iaeiaei, noaoenoe/anee aeinoiaa?iuo ?acee/ee a
eeiaoe/aneeo e oa?iaeieiae/aneeo ia?aiao?ao aeaoo auoaoeacaiiuo
eiiiiiaioia enneaaeiaaiiiai oeia oiea iaia?oaeaii ia auei. E?iia oiai
auei iieacaii, /oi iaaeeaiii-eiaeoeae?othueeny eaeeaaue oie DR-oeia
(RBK1), ii naiei ia?aiao?ai aiaeiae/iue auoaiienaiiiio DR-oieo, oae aea
oa?aeoa?ecoaony aeaooyeniiiaioeeaeueiui oiaeii a?aiaiiie eiaeoeaaoeee n
iinoiyiiuie a?aiaie ii?yaeea 50-100 in e 5-10 n niioaaonoaaiii (Christie
et al., 1989).

Ii?ia aeoeaaoeee eaeeaaiai oiea E-oeia eaaeeo a i?aaeaeao -20 iA,
iioaioeeae iieiaeiiie aeoeaaoeee ninoaaeyao +15 iA. E-oie aeoeae?oaony
iaaeeaiii n iinoiyiiie a?aiaie aeanyoee ieeeenaeoiae e ia eiaeoeae?oaony
ii e?aeiae ia?a a oa/aiea 10-15 n i?e iinoiyiiii o?iaia aeaiiey?ecaoeee
iaia?aiu. Iaeiaeoeae?othueeny eaeeaaue oie ia aue /oanoaeoaeai e
ieeeeiiey?iui eiioeaio?aoeeyi 4-AI, iaeiaei aeiee?iaaeny 10iI OYA ia
70-80%. Enneaaeiaaiey a iaeanoe iieaeoey?iie aeieiaee (Stuhmer et al.,
1989) iaia?oaeeee o?e oeia aaiia, eiaee?othueo eaeeaaua eaiaeu
caaea?aeaiiiai aui?yieaiey ni naienoaaie, aeeceeie e naienoaai
enneaaeiaaiiiai oeia E-oiea: Kv1.2 (RCK2), Kv1.1 (RCK1) e Kv1.5 (RCK5).
Yoe eaiaeu iaeaaeatho noiaeiuie eeiaoe/aneeie ia?aiao?aie, ii
ioee/athony ii oa?iaeieiae/aneie /oanoaeoaeueiinoe e OYA. IC50 aeey
RCK1, RCK2 e RCK5 eaiaeia ninoaaeyao niioaaonoaaiii 0.6, 7 e 129 iI.
Iiyoiio, enneaaeiaaiiue eaeeaaue oie caaea?aeaiiiai aui?yieaiey,
iaeaieaa aa?iyoii, ii?aaeaeyaony Kv1.2 oeiii eaeeaaiai eaiaea.

Enneaaeiaaiey eciaiaiee eaeeaaie i?iaiaeeiinoe niiaoe/aneie iaia?aiu
naini?iuo iae?iiia iieacaee, /oi n?aaeiea ieioiinoe auno?i- e
iaaeeaiii-eiaeoeae?othueony oieia oaaee/eaathony a oa/aiee ia?auo iyoe
aeiae iinoiaoaeueiiai ?acaeoey e ia eciaiythony a neaaeothuea aeanyoue
aeiae. N?aaeiyy ieioiinoue iaeiaeoeae?othuaainy eaeeaaiai oiea
caaea?aeaiiiai aui?yieaiey oiaiueoaaony a ia?aue e ia eciaiyaony ai
aoi?ie enneaaeiaaiiue ia?eiae ?aiiaai iiniaoaeueiiai ?acaeoey. I?e yoii,
eiee/anoai iae?iiia, eiathueo ieioiinoue auno?i-eiaeoeae?othuaainy
eaeeaaiai oiea aieaa 20 ?A/?O, oaaee/eaaaony a i?ioeanna iioiaaiaca. A
oi aea a?aiy, eiee/anoai iae?iiia, eiathueo ieioiinoue
iaeiaeoeae?othuaainy eaeeaaiai oiea aieueoa 25 ?A/?O, oiaiueoaaony a
oa/aiee ?aiiaai iioiaaiaca. I/aaeaeii, /oi eciaiaiea ieioiinoe eaeeaauo
eaiaeia i?eaiaeeo e eciaiaieth aeeeoaeueiinoe iioaioeeaea aeaenoaey, /oi
a naith i/a?aaeue aea/ao ca niaie aa?eaoeeth a eiee/anoaa eaeueoeey,
i?iieeathuaai aioo?ue eeaoee ai a?aiy i?ioiaeaeaiey iioaioeeaea
aeaenoaey. Iniaoth ?ieue a yoii niunea ea?atho eaeeaaua eaiaeu,
?aniieiaeaiiua iaiin?aaenoaaiii a iaeanoe i?aneiaioe/aneiai ieii/aiey
iae?iia. Eciaiaiey oi?iu iioaioeeaea aeaenoaey a yoie iaeanoe e
niioaaonoaothuaa eciaiaiea eiee/anoaa i?iieeathuaai aioo?ue iaia?aiu
eaeueoeey iiaoo iaiin?aaenoaaiii aeeyoue ia i?aneiaioe/aneee iaoaieci
aua?ina iaaeeaoi?a.

Eniieuecoy iaoiae aiaeeaoi/iie yeaeo?e/aneie noeioeyoeee a oneiaeyo
ionoonoaey aaia?aoeee iioaioeeaea aeaenoaey (a OOO — niaea?aeauai
?anoai?a), auei enneaaeiaaii aeeyiea eciaiaiee eaeeaaie i?iaiaeeiinoe
i?aneiaioe/aneie iaia?aiu, i?eiaiyy aeieaoi?u eaeeaauo eaiaeia, ia
oi?iiciua iinoneiaioe/aneea oiee iae?iiia aeiiieaiia ia o?iaia
ioaeaeueiiai neiaioe/aneiai ieii/aiey. Iieacaii, /oi a OOO-niaea?aeauai
?annoai?a eciaiaiea eaeeaaie i?iaiaeeiinoe iaia?aiu iaeeii/iie oi?iiciie
neiaioe/aneie oa?ieiaee (iiae aeaenoaeai oao?ayoeeaiiiiey eee
4-aieiiie?eaeeia) i?eaiaeeo e oaaee/aieth aiieeooaeu iinoneiaioe/aneiai
ioaaoa i?e iaeciaiiuo ia?aiao?ao aiaeeaoi/iiai noeioea. I?iaaaeaiiue
eaaioiaue aiaeec oi?iiciie neiaioe/aneie ia?aaea/e iieacae, /oi
eciaiaiea iinoneiaioe/aneiai ioaaoa iiae aeaenoaeai aeieaoi?ia eaeeaauo
eaiaeia i?ienoiaeeo ca n/ao oaaee/aiey eaaioiaiai niaea?aeaiey aua?ina
iaaeeaoi?a ec ioaeaeueiie neiaioe/aneie oa?ieiaee i?e iaeciaiiie
aaee/eia iaeiiai eaaioa.

Eeth/aaua neiaa: eaeeaaua eaiaeu, iioiaaiac, neiaioe/aneay ia?aaea/a,
eaaioiaue aiaeec.

Vasilyev D. V. Voltage-gated potassium currents of neurons of rats:
ontogenesis and role in inhibitory synaptic transmission. — Manuscript.

Thesis for PhD degree by specialty 03.00.02 — Biophysics. — Bogomoletz
Institute of Physiology, Kiev, 1998.

The dissertation is devoted to investigation of the properties of
voltage-gated potassium currents of neurons of rat during early
postnatal development. The obtained results indicated that kinetic,
steady-state and pharmacological properties of A-, DR- and K-types of
potassium currents of DRG neurons did not differ significantly from that
of hippocampal neurons. Mean densities of A- and DR- currents of DRG
neurons increased while mean density of K-current decreased during first
five days of postnatal development and did not change thereafter.
Further investigation showed that in TTX-containing solution changes in
potassium conductance of a single presynaptic terminal of cultured
hippocampal neurons due to action of potassium channel blockers TEA or
4-AP lead to the increasing of the mean quantal content of transmitter
release and did not change the value of a single quantum.

Key words: potassium channels, ontogenesis, synaptic transmission,
quantal analysis.

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