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

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

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Eaei Oeyia Aieiaeeie??aia

OAeE 577.352:612.822

CI?IE IAOAI?CI?A IO?EIA?A?*II? EAEUeOe??AI? NEAIAE?CAOe?? A IAE?IIAO
NAINIIIOI?II? EI?E UO??A A IINOIAOAEUeIIIO IIOIAAIAC?

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.

?iaioo aeeiiaii o a?aeae?e? caaaeueii? o?c?ieia?? ia?aiai? nenoaie

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

Iaoeiaee ea??aiee: aeaaeai?e IAI Oe?a?ie EINOTHE Ieaoii A?eai?iae/

Io?oe?ei? iiiiaioe: aeieoi? a?ieia?/ieo iaoe, aeaaeai?e IAI Oe?a?ie

E?eooaeue Ieaa Ieaenaiae?iae/,

aeieoi? iaaee/ieo iaoe

NIEIAEIA Aiaoie?e ?aaiiae/

I?ia?aeia onoaiiaa: eaoaae?a a?io?ceee Ee?anueeiai Iaoe?iiaeueiiai

Oi?aa?neoaoo ?i. Oa?ana Oaa/aiea.

Caoeno a?aeaoaeaoueny «_27__» __ea?oiy___1999 ?. ia can?aeaii?
niaoe?ae?ciaaii? a/aii? ?aaee Ae26.198.01 i?e ?inoeooo? o?c?ieia??

?i. I.I.Aiaiiieueoey IAI Oe?a?ie ca aae?anith:

252024 i.Ee?a-24, aoe. Aiaiiieueoey, 4.

C aeena?oaoe??th iiaeia iciaeiieoenue a a?ae?ioaoe? ?inoeoooo

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

Aaoi?aoa?ao ?ic?neaiee «__26__» _ethoiai_1999 ?.

A/aiee nae?aoa?

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

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

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

Aeooaeuei?noue i?iaeaie. Aioo??oiueiee?oeiiee eaeueoe?e ? iaea?eueo
oi?aa?naeueiei ?aaoeyoi?ii ee?oeiieo ooieoe?e. Ci?ie oeeoiieaciaoe/ii?
eiioeaio?aoe?? eaeueoe?th ([Ca2+]i) caaacia/othoue ia?aaea/o neaiae?a
a?ae no?oeoo? ieaciaoe/ii? iaia?aie aei aioo??oiueiee?oeiieo nenoai,
caioneath/e ?yae aaaeeeaeo i?ioean?a, ui eaaeaoue a iniia? ee?oeiii?
caoaeaeoaaiino?, nae?aoe??, ?aaoeyoe?? aaiaoe/iiai aia?aoa, iaoaaie?/ieo
i?ioean?a. ?aaoethaaiiy ??aiy [Ca2+]i caaacia/o?oueny ooieoe?iiaeueiith
aeoeai?noth ye no?oeoo? ieaciaoe/ii? iaia?aie, oae ?
aioo??oiueiee?oeiieo i?aaiae. A ia?aiaeo ee?oeiao OeIN iniiai? ia?aiao?e
oeeo nenoai, ?o aca?iiae?y oa ci?ie i?ae /an iioiaaiaco aea/ai?
iaaeinoaoiuei. Iauiaeaaii aoei iieacaii, ui AOO iiaea aeae?eyoenue ye
noiooi?e iaae?aoi? c i?aneiaioe/ieo oa?i?iaeae a aaaaoueio a?aeae?eao
OeIN, oiio ieoaiiy i?i ?nioaaiiy ?aoeaioi??a aei iicaee?oeiiiai AOO,
io?eia?a?/iiai eiiiiiaioa eaeueoe??ai? neaiae?caoe?? ? aaaeeeaei aeey
?icoi?iiy iaoai?ci?a i?aeee?oeiii? aca?iiae??. Ae?y iicaee?oeiiiai AOO
ye iae?io?aini?oa?a a oeaio?aeueieo iae?iiao a cia/i?e i??? ua ia
aea/aia. I?i iaoai?cie io?eia?a?/ii? eaeueoe??ai? neaiae?caoe?? a
iae?iiao OeIN, a oaeiae i?i ?o iioiaaiaoe/i? ci?ie aeaieo i?aeoe/ii
iaia?.

Iaoith ?iaioe aoei aeine?aeaeaiiy io?eia?a?/ii? eaeueoe??ai?
neaiae?caoe?? a iae?iiao nainiiioi?ii? ei?e uo??a, cie?aia ?ie?
io?eii?aoeaioi?ii? nenoaie a oeueiio i?ioean? oa iioiaaiaoe/ieo ci?i o
a?aeiia?aeieo iaoai?ciao.

Aieiai? caaaeaiiy.

1. Aeine?aeeoe aeanoeaino? ?iii- oa iaoaaio?iiii? io?eia?a?/ii?
eaeueoe??ai? neaiae?caoe?? a iae?iiao nainiiioi?ii? ei?e uo??a ??ciiai
a?eo.

2.Aeine?aeeoe aeanoeaino? ?iiceoieo?eoinoao-/ooeeaiai aeaii oa eiai
o/anoue a io?eia?a?/i?e eaeueoe??a?e neaiae?caoe?? a oeacaieo iae?iiao.

3. Aeine?aeeoe aeanoeaino? eioa?i-/ooeeaiai eaeueoe??aiai aeaii a
iae?iiao nainiiioi?ii? ei?e uo??a ??ciiai a?eo.

Iaoeiaa iiaecia io?eiaieo ?acoeueoao?a. Aeyaeaii ooieoe?iiaeueii
aaaeeea? iaoai?cie, ui aa?ooue o/anoue o ?aaoethaaii? ??aiy
oeeoiieaciaoe/ii? eiioeaio?aoe?? ?ii?a eaeueoe?th a iae?iiao
nainiiioi?ii? ei?e uo??a ??cieo a?eiaeo a?oi. Aia?oa anoaiiaeaii
?nioaaiiy ?iii- oa iaoaaio?iiieo iaoai?ci?a io?eia?a?/ii? eaeueoe??ai?
neaiae?caoe?? a oeacaieo iae?iiao. Iienaii aeanoeaino?
aioo??oiueiee?oeiiiai ?iiceoieo?eoinoao-/ooeeaiai eaeueoe??aiai aeaii a
iae?iiao nainiiioi?ii? ei?e uo??a ??cieo a?eiaeo a?oi, aea/aii
iioiaaiaoe/i? iniaeeaino? ooieoe?iioaaiiy eioa?i-/ooeeaiai
aioo??oiueiee?oeiiiai eaeueoe??aiai aeaii a oeeo iae?iiao. Iienai?
ca’ycee i?ae ??cieie eaeueoe??aeie aeaii aiaeiieaciaoe/iiai ?aoeeoeoio a
oeacaieo iae?iiao.

Oai?aoe/ia ? i?aeoe/ia cia/aiiy ?iaioe. ?acoeueoaoe ?iaioe iathoue
ooiaeaiaioaeueia cia/aiiy, ine?eueee aeicaieythoue ioe?ieoe aianie
??cieo aioo??oiueiee?oeiieo nenoai, ui aa?ooue o/anoue a oiie?e
?aaoeyoe?? ??aiy oeeoiieaciaoe/ii? eiioeaio?aoe?? ?ii?a eaeueoe?th ia
??cieo aoaiao ?icaeoeo iae?ii?a nainiiioi?ii? ei?e. I?aeoe/ia oe?ii?noue
?iaioe iieyaa? a oiio, ui aeyaeaii iniaeeaino? eaeueoe?e-?aaoethth/eo
nenoai aeaieo iae?ii?a a i?ioean? iioiaaiaco, ui iiaea aooe aaaeeeaei
aeey ei?aeoe?? ii?ooaiue ooieoe?iiaeueiiai noaio ia?aiai? nenoaie a
i?ioean? ?icaeoeo.

Iniaenoee aianie caeiaoaa/a. I?aeaioiaea i?aia?aoo, oa?aoaaiiy c??c?a
oeoi?anoeaioiei aa?aieeii ? an? aenia?eiaioe ii ?a?no?aoe?? eaeueoe??aeo
o?aice?io?a aoee aeeiiai? aaoi?ii iniaenoi. A iaaiai?aii? ?acoeueoao?a
aeoeaio o/anoue a?aee ni?aaaoi?e ae?oeiaaieo i?aoeue.

Ai?iaaoe?y ?iaioe. Iniiai? iieiaeaiiy aeena?oaoe?? aeiiia?aeaeenue ?
iaaiai?thaaeenue ia nai?ia?ao ?inoeoooo o?c?ieia?? ?i. I.I. Aiaiiieueoey
IAIO (1997-1998), i?aeia?iaeiiio nai?ia?? ”Aioo??oiueiee?oeiia
neaiae?caoe?y” (Ee?a, 1997), OV c’?cae? Oe?a?inueeiai o?c?ieia?/iiai
oiaa?enoaa (Aeiiaoeuee, 1998), I Oe?a?inuee?e eiioa?aioe?? iae?iiaoe (
Ee?a, 1998).

Ioae?eaoe??. Ca oaiith aeena?oaoe?? iioae?eiaaii 6 ?ia?o, a oiio /ene? 4
noaoo? oa 2 oac.

Ianya oa no?oeoo?a aeena?oaoe??. Aeena?oaoe?y neeaaea?oueny c anooio,
nieneo nei?i/aiue, iaeyaeo e?oa?aoo?e, iieno iaoa??ae?a ? iaoiae?a
aeine?aeaeaiue, ?acoeueoao?a aeine?aeaeaiue, iaaiai?aiiy ?acoeueoao?a,
aeniiae?a oa nieneo e?oa?aoo?e c 207 iaeiaioaaiue. ?iaioa aeeeaaeaia ia
117 noi??ieao, ?ethno?iaaia 17 ?enoieaie oa 2 oaaeeoeyie.

IAOA??AEE OA IAOIAeE AeINE?AeAEAIUe

I?aeaioiaea i?aia?aoo. Aeine?aeaeaiiy i?iaiaeeeenue ia iae?iiao II-III
oa??a a oiieeo c??cao iiceo uo??a aeae?eueeio a?eiaeo a?oi: iieiaeeo (14
aei?a), i?aeoe/ii c??eeo (21 aeaiue) oa aei?ineeo (1 i?nyoeue). I?ney
aeaeai?oaoe?? iicie caio?thaaany o oieiaeiee nieueiaee ?ic/ei (0 — 40N)
? iiae?eyany ia 2 i?aeoe?. I?ioeaaeo?a a?ae ii/aoeo aeaeai?oaoe?? aei
?icae?eaiiy iiceo i?iaeiaaeoaaeany ia a?eueoa 60-90 naeoiae. Iio?i iaeia
c i?aeoeue i?eeeathaaeany iie?ae?eeai?aeiei eea?i aei i?aeeiaeee
a?a?ioiia (Campden, Campden Instrument LTD, U.K.); eaia?a a?a?ioiia
caeeaaeanue oieiaeiei nieueiaei ?ic/eiii. C??ce ia??coaaeenue
naa?oaeueii 200-250 iei caaoiaoee; oaeaee?noue iiaea/? eaca — 1 ni/n,
/anoioa eieeaaiue — 11 Aoe. I?ney ia??coaaiiy c??ce aeo?eioaaee a
?ic/ei?, iane/oaaiiio ea?a?aaiii (5% NI2 + 95% I2). Ia?aae
caaaioaaeaiiyi oeoi?anoeaioiei aa?aieeii c??ce aeo?eioaaeenue 20 oaeeei
i?e oaiia?aoo?? 300N. I?ney i?ioeaaeo?e oa?aoaaiiy ? aei ii/aoeo
aenia?eiaio?a c??ce aeo?eioaaee i?e e?iiaoi?e oaiia?aoo?? (20-220N) ia
iaioa 1 aiaeeie. sse?noue io?eiaieo c??c?a aeicaieyea i?iaiaeeoe
aeine?aeaeaiiy i?ioyaii 4-6 aiaeei. Ae?eyiee nainiiioi?ii? ei?e aoee
?aeaioeo?eiaai? ca noa?aioaene/iei aoeanii (Paxinos & Watson, 1944).

Oeoi?anoeaioia aei??thaaiiy aioo??oiueiee?oeiii? eiioeaio?aoe?? ?ii?a
eaeueoe?th. Aeey aei??thaaiiy aioo??oiueiee?oeiii? eiioeaio?aoe?? ?ii?a
eaeueoe?th a iae?iiao nainiiioi?ii? ei?e aeei?enoiaoaaee
iaia?aiii?iieeio oi?io oeoi?anoeaioiiai aa?aieea Fura-2/AM. Aeey eiai
caaaioaaeaiiy c??ce ?ieoaoaaee a ?ic/ei?, ui i?noea anoa?eo?eiaaio oi?io
aa?aieea Fura-2/AM a eiioeaio?aoe?? 5 ieI, ?ic/eiaio a
aeeiaoeenoeueoieneae? c aeiaeaiiyi aeaoa?aaioo Pluronic F-127 (0,02%). A
oae?e oi?i? aa?aiee i?ioiaeeoue a ee?oeio, iio?i aiaeiaaiieie anoa?acaie
ao??i? a?oie a?aeie?aieththoueny, ciiae noa? ca?yaeaeaiei ? caeeoeoe
ee?oeio ia iiaea. Oa?aoaaiiy i?iaiaeeeinue i?e oaiia?aoo?? 350N 35
oaeeei aeey 14-e 21-aeaiieo uo??a ? 20 oaeeei aeey c??c?a iaeii
-i?ny/ieo oaa?ei. Iioe/ia /anoeia onoaiiaee caaacia/oaaea caoaeaeaiiy
oeoi?anoeaioe?? ciiaea i?e aeiaaeeiao oaeeue 3605 ? 3905 ii ?
?a?no?aoe?th eiai ai?n?? i?e 5305 ii ca aeiiiiiaith oioiiiiiiaeoaa/a.
Iniiaieie aeaiaioaie aenia?eiaioaeueii? onoaiiaee aeey aeaioaeeueiaiai
aei??thaaiiy eiioeaio?aoe?? ?ii?a eaeueoe?th aoee: aeaea?aei na?oea
(?oooia eaiia iiooaei?noth 50 Ao), nenoaia ci?ie o?eueo??a (eieani c
aiiioiaaieie o?eueo?aie, ui iaa?oaeinue c? oaeaee?noth 5 Aoe), i?e?ineii
(Axioskop, Zeiss), iiaeoeue iiia?aaeiuei? ia?iaee neaiae?a, ui oaeiae
ea?oaaa ci?iith o?eueo??a (Luigs und Neumann, I?ia//eia) ? eiii’thoa?.

Aei??thaaiiy oeoi?anoeaioe?? i?e caoaeaeaii? na?oeii c aeaiia
aeiaaeeiaie oaeeue aeicaiey? eaaei ?ic?aooaaoe [Ca2+]i a ee?oei? ca
oi?ioeith (Grynkiewicz et al., 1985):

[Ca2+]i= Kd * b * (R — Rmin)/(Rmax-R),

aea Ed — eiinoaioa aeenioe?aoe?? eiiieaeno Fura-2 n eaeueoe??i (224
iiieue/e), R=F360/F390 – iioi/ia a?aeiioaiiy oeoi?anoeaioieo neaiae?a,
Rmin = F360/F390|Ca0 — oa ae a?aeiioaiiy a ?ic/ei? c iecueeith
eiioeaio?aoe??th Ca2+, Rmax = F360/F390|Ca — oa ae a?aeiioaiiy a ?ic/ei?
c aenieith eiioeaio?aoe??th Ca2+, b = F390|Ca0/F390|Ca — a?aeiioaiiy
oeoi?anoeaioieo neaiae?a a iecuee?e ? aenie?e eiioeaio?aoe?? Ca2+ i?e
caoaeaeaii? na?oeii c aeiaaeeiith oaee? 390 ii. Ia?aiao?e Rmin, Rmax ? b
aecia/aee aenia?eiaioaeueii a e?aieyo icia/aieo aeua ?ic/ei?a, ui
?icoaoiaoaaeenue ia aei? aenia?eiaioaeueii? eaia?e. A ?acoeueoao? aeey
iaoi? nenoaie io?eiaee — Rmin= 0.6, Rmax= 4 oa b=13.8.

?ic/eie. I?e ?iaio? c? c??caie an? ?ic/eie aiooaaeenue ia iniia? oaeiai
?ic/eio (a iiieue/e): NaCl — 135, KCl — 5.4, MgCl2 — 1, CaCl2 — 2.5,
NaHCO3 — 16, KH2PO4 — 1.6, aetheica — 10, iino?eii iane/oaaiee
ea?aiaaiii (pH=7.4). Aaceaeueoe??aee ?ic/ei aiooaaany aea?iiey?iith
cai?iith CaCl2 ia MgCl2 oa aeiaeaaaiiyi 1 iiieue/e EGTA; ?ic/eie c
i?aeaeuaiei ai?noii eae?th aai eioa?io – cai?iith NaCl ia a?aeiia?aeio
e?euee?noue KNl aai eioa?io. Ci?ia ?ic/ei?a i?iaiaeeeanue i?ioieii,
oaeaee?noue yeiai ?aaoethaaeanue a?ae 10 aei 20 ie/oa. Ia’?i
aenia?eiaioaeueii? eaia?e aei??aithaaa 0.5 ie. An? aenia?eiaioe aoee
i?iaaaeai? i?e oaiia?aoo?? 320N.

?ACOEUeOAOE AeINE?AeAEAIUe

?nioaaiiy io?eia?a?/ii? eaeueoe??ai? neaiae?caoe?? a iae?iiao
nainiiioi?ii? ei?e iiceo uo??a.

Aie?eaoe?y AOO a eiioeaio?aoe?yo a?ae 5 aei 2000 ieI i?ecaiaeeea aei
o?aice?ioiiai ca?eueoaiiy [Ca2+]i a a?eueoino? iae?ii?a nainiiioi?ii?
ei?e ye 14-, oae ? 30-aeaiieo uo??a. Oaea ae?y AOO iiaea aooe
iiina?aaeeiaaia iinoneiaioe/ieie ?iii- oa iaoaaio?iiieie
io?eii?aoeaioi?aie aai AOO-?iaeoeiaaiei aea?eueiaiyi ?ioiai
iae?io?aini?oa?a c i?aneiaioe/ii? oa?i?iae?. Iaeiae, i? aiie?ooaea, i?
e?iaoe/i? oa?aeoa?enoeee eaeueoe??aeo o?aice?io?a a iae?iiao iaio
a?eiaeo a?oi cia/ii ia ci?ithaaeenue a i?enooiino? aioaaii?no?a
aeooaiaoieo ?aoeaioi??a d-APV (25 ieI) ? CNQX (20 ieM), a oaeiae i?e
?ieoaaoe?? c??co a ?ic/ei?, ui i?noeoue OOO a eiioeaio?aoe?? 1 ieI .

Oaeei /eiii, ie iaee i?aenoaae aaaaeaoe, ui ca?eueoaiiy [Ca2+]i i?e
aie?eaoe?? AOO aeeeeeaia cia/iith i??ith aeoeaaoe??th io?eia?a?/ieo
?aoeaioi??a aea?aii? ee?oeie.

Aioaaii?noe io?eii?aoeaioi??a – ??ADS (20 ieI) ? no?ai?i (100 ieI)
ciaiooaaee aiie?ooaee eaeueoe??aeo AOO-?iaeoeiaaieo a?aeiia?aeae a iaio
a?oiao iae?ii?a ia 26%10% (n=6) ? 56%12% (n=5) a?aeiia?aeii.

Aeey aecia/aiiy oeio io?eii?aoeaioi??a, aeni?aniaaieo a iae?iiao
nainiiioi?ii? ei?e uo??a, ie aecia/eee ?yaee aoaeoeaiinoae aiaeia?a AOO
a eiioeaio?aoe?yo 100 ieI. Aiie aoee oaeeie: a iae?iiao 14-aeaiieo uo??a
— ATOgS>AOO=AAeO>>AMO> Aaeaiicei » a,b-methyleneATO»OOO; a aeey
30-aeaiieo — ATOgS>AOO> AAeO a,b-methylene ATO>AaeaiiceiOOO, AMO. Oae?
?yaee aoaeoeaiinoae aeicaieythoue i?eionoeoe o/anoue ia?aaaaeii ?2O oeio
?aoeaioi??a (Burnstock G. et al., 1985). Iaiao?aeii a?aei?oeoe, ui a 1/3
aeine?aeaeaieo ee?oei iaio a?oi ie niinoa??aaee iii?oia ca?eueoaiiy
[Ca2+]i i?e aie?eaoe?? 100 ieI aaeaiiceia.

Iaoai?cie io?eia?a?/ii? eaeueoe??ai? neaiae?caoe?? a iae?iiao
nainiiioi?ii? ei?e 14-aeaiieo uo??a. Aiie?ooaee AOO-?iaeoeiaaieo
eaeueoe??aeo o?aice?io?a aoee aeica-caeaaeieie a ae?aiacii?
eiioeaio?aoe?e a?ae 5 aei 2000 ieI. sseui aiie?ooaeo eaeueoe??ai?
a?aeiia?ae?, aeeeeeaii?

i?eeeaaeaiiyi 2000 ieI AOO, i?eeiyoe ca iaeeieoeth, caeaaei?noue iiaea
aooe i?aaenoaaeaia a aeaeyae? neaii?aeaeueii? e?eai?, ui iieno?oueny
??aiyiiyi

[Ca2+]i = [Ca2+]i max [ATP]/([EN50+[ATP])m, aea m=1.06 ? EN50= 72 ieM.

?iiceoieo?eoinoao-/ooeeaa aeaii. Aeey aecia/aiiy aeaea?aea Ca2+ ie
i?eeeaaeaee AOO a aaceaeueoe??aiio ?ic/ei?. Iayai?noue cia/ii?
a?aeiia?ae? a 90% iae?ii?a 14-aeaiieo oaa?ei i?e a?aenooiino? ?ii?a
eaeueoe?th a ciai?oiueiee?oeiiiio ?ic/ei? aiai?eoue i?i oa, ui aeai?
iae?iie iathoue iaoaaio?iii? io?eii?aoeaioi?e, aeoeaaoe?y yeeo aeeeeea?
ca?eueoaiiy [Ca2+]i oeyoii aea?eueiaiiy Ca2+ c aioo??oiueiee?oeiieo
aeaii. Iaeiae, aaea ae?oaa aie?eaoe?y AOO a aaceaeueoe??aiio ?ic/ei?
aeeeeeaea a?aeiia?aeue, aiie?ooaea yei? aoea ia 52%7% iaioith ca ia?oo

(n=11). O?aoy aai /aoaa?oa aie?eaoe?? i?aeoe/ii ia i?ecaiaeeee aei
ca?eueoaiiy [Ca2+]i. ?ieoaaoe?y c??co i?ioyaii 5 oaeeei a ?ic/ei?, ui
i?noea 1 ieI oaineaa?a?ia, niaoeeo?/iiai aeieaoi?a eaeueoe??aeo AOOac
A?, i?ecaiaeeea aei cieeiaiiy AOO-?iaeoeiaaii? a?aeiia?ae? a
aaceaeueoe??aiio ?ic/ei? (n=5) .

?iiio?iii? iaoai?cie io?eia?a?/ii? eaeueoe??ai? neaiae?caoe??. Ie
aie?eoaaee 100 ieI AOO aeae?eueea ?ac?a i?ae?yae c ?ioa?aaeii 60
naeoiae. Aiie?ooaee ae?oai? oa ianooiieo eaeueoe??aeo a?aeiia?aeae aoee
iaioa ia?oi? ia 30%4% (n=9). Oea ciaioaiiy iiaea aooe aeeeeeaii a)
aeanaineoecaoe??th io?eii?aoeaioi??a oa/aai a) ciaioaiiyi aianeo
iaoaaio?iiiiai eiiiiiaioo (nionoioaiiyi aioo??oiueiee?oeiieo
caianiee?a). I?e iine?aeiaieo aie?eaoe?yo AOO a i?enooiino? 1 ieI
oaineaa?a?io aiie?ooaea o?aoueiai oa ne?aeoth/eo eaeueoe??aeo
o?aice?io?a caeeoa?oueny noaeith ? aei??aith? 65%8% a?ae eiio?ieueii?
(n=13). I/aaeaeii, ui naia oe? [Ca2+]i o?aice?ioe ? aeeeth/ii
?iiio?iiiith /anoeiith eaeueoe??ai? a?aeiia?ae?. Ioaea, i?e iine?aeiaieo
i?eeeaaeaiiyo AOO, ii/eiath/e c 3-i? aie?eaoe?? ?iiio?iiia /anoeia
eaeueoe??aiai o?aice?ioa aei??aith? 65%, a aeiey iaoaaio?iiii? /anoeie
ciaioo?oueny c

63% (ioe?ithth/e iaeneiaeueiee aianie iaoaaio?iiieo io?eii?aoeaioi??a ca
aaee/eiith aiie?ooaee ia?oi? eaeueoe??ai? a?aeiia?ae? a aaceaeueoe??aiio
?ic/ei?) aei 35%. Oea iiaea aooe iia’ycaii c oei, ui a)
aioo??oiueiee?oeii? aeaii ia?acaiiaiththoueny ia iiai?noth i?e
iine?aeiaieo aie?eaoe?yo c 60-naeoiaeiei ?ioa?aaeii ?, oaeei /eiii,
ciaioo?oueny e?euee?noue ?iiia Ca2+, caeaoieo aei aea?eueiaiiy i?e
aeoeaaoe?? iaoaaio?iiieo io?eii?aoeaioi??a; a) iiaeeeai, a?aeaoaa?oueny
aeanaineoecaoe?y ?2O ?aoeaioi??a; a) iiaeeeai, ?niothoue a?aei?iiino? a
ooieoe?iioaaii? iaoai?ci?a aioo??oiueiee?oeiii? eaeueoe??ai?
iia?e?caoe?? a ii?iaeueiiio ? aaceaeueoe??aiio ?ic/eiao ?, a neeo
oeueiai, iaei?aeoii aeei?enoiaoaaoe aaee/eio aiie?ooaee eaeueoe??aiai
o?aice?ioa a aaceaeueoe??aiio ?ic/ei? aeey ioe?iee aianeo iaoaaio?iiieo
?aoeaioi??a a caaaeuei?e a?aeiia?ae? a ii?iaeueiiio ?ic/ei?.

Oaeei /eiii, a iae?iiao nainiiioi?ii? ei?e 14-aeaiieo uo??a ca?eueoaiiy
[Ca2+]i i?e aie?eaoe?? AOO a?aeaoaa?oueny i?e aeoeaaoe?? ye
iaoaaio?iiieo, oae ? ?iiio?iiieo io?eii?aoeaioi??a. Aea a oeueiio
i?ioean? iiaeooue a?aoe o/anoue ? iioaioe?ae-ea?iaai? eaeueoe??a?
eaiaee, ine?eueee no?oi ?ii?a /a?ac ianaeaeoeai? ?iii? eaiaee i?e
aeoeaaoe?? ?2O ?aoeaioi??a iiaea aeeeeeaoe ci?uaiiy iaia?aiiiai
iioaioe?aeo. Ae?enii, aeieaoi?e iioaioe?ae-ea?iaaieo eaeueoe??aeo
eaiae?a aa?aiai?e (100 ieI), i?oaae?i?i (100 ieI) oa Ni2+ (50 ieI)
ciaiooaaee aiie?ooaeo eaeueoe??aiai o?aice?ioo, aeeeeeaiiai aie?eaoe??th
100 ieI AOO, ia 28%8% (n=7), 23%8% (n=7) e 17%6%( n=9) a?aeiia?aeii. Oe?
aeai? i?aeoaa?aeaeothoue o/anoue ye aeniei- , oae ? iecueeiii?iaiaeo
iioaioe?ae-ea?iaaieo eaeueoe??aeo eaiae?a a oi?ioaaii? eaeueoe??aeo
o?aice?io?a i?e aie?eaoe?? AOO.

Eioa?i-/ooeeaa aeaii. Ca?eueoaiiy [Ca2+]i iiaea aeeeeeaoe
eaeueoe?e-?iaeoeiaaia aea?eueiaiiy eaeueoe?th (CICR) c eioa?i-/ooeeaiai
aeaii. Iaeiae, 10-20 naeoiaei? aie?eaoe?? eioa?io a eiioeaio?aoe?yo aei
40 iI ia i?ecaiaeeee aei ca?eueoaiiy aioo??oiueiee?oeiiiai eaeueoe?th a
90% aeine?aeaeoaaieo iae?ii?a (23 c 26), iaa?oue i?e i?aeaeuaii?e
[Ca2+]i. Aiie?ooaee a?aeiia?aeae ia ia?i? aie?eaoe?? a?ia?eae??aiai
?ic/eio (50 iI ENl) a eiio?ie? ? a ?ic/ei?, ui i?noeoue 1ieI
oaineaa?a?io, aoee iaeiaeiaeie. Oe? aeai? aeicaieythoue i?eionoeoe, ui
yeui oaeee caianiee ? ?nio? a iae?iiao II-III oa??a nainiiioi?ii? ei?e
14-aeaiieo uo??a, oi eiai ooieoe?iiaeueia ?ieue ia aeaiiio aoai?
?icaeoeo iacia/ia.

Iioiaaiaoe/i? ci?ie iaoai?ci?a eaeueoe??ai? neaiae?caoe??

a iae?iiao nainiiioi?ii? ei?e uo??a.

Ao?ae eaeueoe?th ii iioaioe?ae-ea?iaaieo eaiaeao ieaciaeaie. Aianie a
eaeueoe??ao neaiae?caoe?th ??cieo oei?a eaiae?a iiaea aeoaea
ci?ithaaoenue a iioiaaiac? (Kostyuk et al., 1993;Tarasenko et al.,
1998). Ie aeei?enoiaoaaee aeieaoi?e iioaioe?ae-ea?iaaieo eaeueoe??aeo
eaiae?a ia?aae oa i?ae /an i?eeeaaeaiiy a?ia?eae??aiai ?ic/eio.
?acoeueoaoe ynii aeaiiino?othoue nooo?a? a?aei?iiino? a aeni?an??
iecueeiii?iaiaeo eaeueoe??aeo eaiae?a i?ioyaii 3-4 oeaei?a
iinoiaoaeueiiai ?icaeoeo: ?o u?euei?noue ciaioo?oueny . Io?eia?a?/ia
eaeueoe??aa neaiae?caoe?y. Aie?eaoe?y AOO a aaceaeueoe??aiio ?ic/ei?
aeeeeeaea i?aeaeuaiiy [Ca2+]i o?eueee a 1/3 oanoiaaieo iae?ii?a
30-aeaiieo uo??a (a 15 c 46). A?eueo oiai, nionoioaiiy
aioo??oiueiee?oeiieo aeaii a?aeaoaaeinue cia/ii oaeaeoa i?ae a iae?iiao
14-aeaiieo oaa?ei. A a?eueoino? aeiaaee?a aaea ae?oaa aie?eaoe?y AOO ia
aeeeeeaea eaeueoe??ai? a?aeiia?ae? .

sseui aeine?aeaeoaaiee iae?ii iaa iaoaaio?iii? io?eii?aoeaioi?e, oi
a?aeiiniee aianie ?iiio?iiieo iaoai?ci?a o a?aeiia?aeue ia ia?oo
aie?eaoe?th AOO aoa, ye ? a iae?iiao 14-aeaiieo uo??a, aeecueei 35%, a
i?e iine?aeiaieo aie?eaoe?yo — ca?eueooaaany, aea ia aei 65% (ye a
iae?iiao iieiaeeo oaa?ei), a o?eueee aei 50% (n=13). Oea iiaea na?ae/eoe
i?i o/anoue ua iaeiiai oeio aioo??oiueiee?oeiiiai aeaii a oi?ioaaii?
eaeueoe??ai? a?aeiia?ae? i?e aie?eaoe?? AOO. Cae/aeii, iaea?eueo
?iia??iei “eaiaeeaeaoii” noaei eioa?i-/ooeeaa aeaii.

Eioa?i-/ooeeaa aeaii. Ae?enii, a 28 c 42 aeine?aeaeaieo iae?ii?a
30-aeaiieo uo??a 5-10 naeoiaeia aie?eaoe?y 20 – 40 iI eioa?io aeeeeeaea
cia/iee [Ca2+]i o?aice?io, i?aeoe/ii iaci?iiee a aaceaeueoe??aiio
?ic/ei?, aea cieeath/ee a i?enooiino? 1 ieI oaineaa?a?io. Nionoioaiiy
eioa?i-/ooeeaiai eaeueoe??aiai aeaii i?ecaiaeeei aei ciaioaiiy aie?ooaee
o?aice?ioa, aeeeeeaiiai a?ia?eae??aith aeaiiey?ecaoe??th ia 325% (n=8).
Oe? aeai? iiaeooue na?ae/eoe i?i iayai?noue aeoeaiiai iaoai?cio CICR i?e
oi?ioaaii? eaeueoe??ai? a?aeiia?ae? a iae?iiao nainiiioi?ii? ei?e
30-aeaiieo uo??a. Aiie?ooaee eioa?i-?iaeoeiaaieo eaeueoe??aeo
a?aeiia?aeae i?e iine?aeiaieo aie?eaoe?yo, ?icae?eaieo 90-naeoiaeieie
?ioa?aaeaie, ciaiooaaeenue iia?eueii: ia 7%, 15%, 14% e 25% a?aeiia?aeii
(n=12) ii??aiyii c ia?oith. A?eueo o?eaaea aie?eaoe?y eioa?io (a?eueoa
30-40 naeoiae) i?ecaiaeeea aei iiaiiai nionoioaiiy aeaii, iaeiae aaea
i?ney 15 naeoiae ?ieoaoaaiiy c??co a ii?iaeueiiio ?ic/ei?, aiie?ooaea
eaeueoe??aiai o?aice?ioo iaeaea aeinyaaea ii/aoeiaiai ??aiy (n=8). Oe?
aeai? aiai?youe i?i oa, ui a c??eeo iae?iiao eioa?i-/ooeea? eaeueoe??a?
aeaii iathoue aaeeeo ?ii?noue ? caeaoi? oaeaeei ia?acaiiaithaaoenue (ia
a?aei?io a?ae IP3-/ooeeaeo aeaii).

Aca?iiae?y eaeueoe??aeo aeaii aiaeiieaciaoe/iiai ?aoeeoeoio

a iae?iiao nainiiioi?ii? ei?e 21-aeaiieo uo??a

A iae?iiao 30-aeaiieo uo??a ie ??aeei iiaee aeyaeoe ee?oeie, ui iaee a ?
?iiceoieo?eoinoao-, ? eioa?i-/ooeeaa aioo??oiueiee?oeii? aeaii. E??i
oiai, ?ii?noue ?iiceoieo?eoinoao-/ooeeaiai aeaii aoea aeoaea iacia/iith.
Naia oiio aeey aea/aiiy aca?iiae?? aioo??oiueiee?oeiieo eaeueoe??aeo
caianiee?a ie i?aoethaaee c ee?oeiaie uo??a “i?ii?aeiiai” a?eo (?21), a
yeeo /ano?oa aoee i?aaenoaaeai? iaeaeaa oeie aeaii. Aeiaaio?eaaea
aie?eaoe?y eioa?io (a?eueoa 30 naeoiae) i?ecaiaeeea aei iiaiiai
nionoioaiiy a?aeiia?aeiiai aioo??oiueiee?oeiiiai ioea. I?e oeueiio
aiie?ooaea AOO-?iaeoeiaaiiai [Ca2+]i o?aice?ioa a aaceaeueoe??aiio
?ic/ei? ciaiooaaeanue ia 34%7% (n=8). A oie aea /an, nionoioaiiy IP3-
/ooeeaiai ioea i?ecaiaeeei aei ciaioaiiy [Ca2+]i o?aice?ioa, aeeeeeaiiai
aie?eaoe??th 40 iI eioa?io ia 62%11% (n=5). Oe? ?acoeueoaoe iiaeooue
aiai?eoe i?i oa, ui a iae?iiao nainiiioi?ii? ei?e ?nio? ooieoe?iiaeueia
aca?iiae?y i?ae ?iiceoieo?eoinoao- oa eaeueoe?e-?iaeoeiaaiei
aea?eueiaiiyi eaeueoe?th, aea iiaeeeai, ui aiie ? aeaiia ??cieie,
i?inoi?iai a?aeie?aieaieie ioeaie.

IAAIAI?AIIss ?ACOEUeOAO?A

A aeai?e ?iaio? i?iaaaeaii aeine?aeaeaiiy iaoai?ci?a
aioo??oiueiee?oeiii? eaeueoe??ai? neaiae?caoe?? a iae?iiao II-III oa??a
nainiiioi?ii? ei?e uo??a in situ, a oiieeo c??cao iiceo. Aeey
aei??thaaiiy eiioeaio?aoe?? [Ca2+]i aoa aeei?enoaiee ia?iaaceaiee iaoiae
caaaioaaeaiiy iae?ii?a iaia?aiii?iieeiith oi?iith oeoi?anoeaioiiai
aa?aieea Fura-2/AM, ui aeicaieeei oieeiooe iaoai?/ieo iioeiaeaeaiue
aioo??oiueiee?oeiieo i?aaiae, ye? aa?ooue o/anoue a aiiainoac?
eaeueoe?th. Aoee ioa?aeoa?eciaai? iniiai? iaoai?cie aaia?aoe??
eaeueoe??aeo neaiae?a a iae?iiao nainiiioi?ii? ei?e uo??a ??cieo
a?eiaeo a?oi, a oaeiae iieacaii ?nioaaiiy ?iii- oa iaoaaio?iiieo
io?eia?a?/ieo iaoai?ci?a caoaeaeaiiy a iae?iiao nainiiioi?ii? ei?e.
?ai?oa aoei anoaiiaeaii, ui a OeIN iaea?eueo iioe?aieie ?iiio?iiieie
io?eii?aoeaioi?aie ? ?2O2, ?2O3, ?2O4 oa ?2O6 oeie (Seguela, 1996;
Vulchanova et al., 1997). Iaeiae, aeyaeaia iaie iecueea /ooeea?noue
io?eii?aoeaioi??a a iae?iiao 14-aeaiieo uo??a PPADS, a?aenooi?noue
cia/ii? aeanaineoecaoe?? iiaea aooe iia’ycaia c aeoeaaoe??th aieiaiei
?2O4 aai ?2O6 ?aoeaioi??a. E??i oiai, oaea i?eiouaiiy
i?aeoaa?aeaeo?oueny oei, ui caaaeyee ?o cia/i?e eaeueoe??a?e
i?ia?aeiino? (Buell, 1996), aeoeaaoe?y naia oeeo oei?a ?aoeaioi??a iiaea
aeeeeeaoe cia/iee ao?ae ?ii?a eaeueoe?th.

Eiioeaio?aoe?y AOO AN50 aeey iae?ii?a a oiieiio c??c? iiceo aeyaeeanue
ia ii?yaeie a?eueoith i?ae aeey eeiiiaaieo ?iiio?iiieo ?aoeaioi??a. Aea
aiia ni?aiaaea? c aeaieie, io?eiaieie ?ai?oa ia aaaaoiee?oeiieo
i?aia?aoao aeaaeaiueeeo i’yc?a (Benham, 1987); a eoeueoeaiaaieo iae?iiao
a?iioaeaiona aiia nyaaea aeecueei 300 ieI (Chen et al.,1994), a AN50
AOO-aeoeaiaaiiai ao?aeiiai no?io a eoeueoeaiaaieo iae?iiao a?iieaiia —
150 ieI (Balachandran & Bennett, 1996).

sse a?aei?/aeiny aeua, ?yaee aoaeoeaiinoae aiaeia?a AOO aeacothoue ia
o/anoue ia?aaaaeii ?2O oeio io?eii?aoeaioi??a, aea ine?eueee iaeaea a
1/3 oanoiaaieo ee?oei ie ?a?no?oaaee cia/i? aaeaiicei-?iaeoeiaai?
eaeueoe??a? o?aice?ioe, iiaeia i?eionoeoe, ui ?nio? noaiiioeyoe?y
iae?ii?a, ui iathoue aaeaiiceiia? (?1) ?aoeaioi?e. Ine?eueee aaeaiicei
ae?? ye ?ia?aoth/ee iae?io?aini?oa?, aeeeeeath/e eae??aee no?oi ?
a?ia?iiey?ecoth/e iaia?aio, iayai?noue 2-o oei?a, ?1 e ?2 ?aoeaioi??a
iiaei a caaacia/eoe iine?aeiaio iiaeoeyoe?th aeoeaiinoae ??cieo
aoi?eiieo iina?aaeiee?a, iia’ycaieo c iaeiei noeioeii – iieaeoeith AOO.

Aeine?aeaeoaai? iae?iie iaiei?oaeno iaee oaeiae iaoaaio?iii?
io?eii?aoeaioi?e, aeoeaaoe?y yeeo caaacia/o? oi?ioaaiiy [Ca2+]i
o?aice?io?a i?e a?aenooiino? ?ii?a eaeueoe?th a ciai?oiueiee?oeiiiio
?ic/ei?. ?ai?oa ?nioaaiiy oaeeo ?aoeaioi??a aoei iieacaii a
eoeueoeaiaaieo iae?iiao a?iieaiia ? oaeaiona (Mironov, 1994), iae?iiao
Io?eei’? iici/ea (in situ)(Kirischuk at al., 1996a), a oaeiae
?cieueiaaieo iae?iiao caaeiueiei??ioeaaeo aaiae??a (Svichar et al.,
1997a). A on?o oeeo aeiaaeeao ae?y iaoaaio?iiieo io?eii?aoeaioi??a
caaacia/oaaeanue ?iaioith ??3-ianaiaea?ii? nenoaie. A iae?iiao
nainiiioi?ii? ei?e uo??a AOO-?iaeoeiaaia aea?eueiaiiy ?ii?a eaeueoe?th
cae?enithaaeinue oaeiae c aeaii aiaeiieaciaoe/iiai ?aoeeoeoio
(aeieoaaeiny oaineaa?a?iii), oiio ie i?eionoeee, ui a aaia?aoe??
eaeueoe??ai? a?aeiia?ae? a aaceaeueoe??aiio ?ic/ei? aa?a o/anoue
IP3-/ooeeaa aeaii. Aeey a?eueo oi/ii? ia?aa??ee aeaiiai i?eiouaiiy ne?ae
aoei a ia?aa??eoe aieea ?ia?a?oi??a oinoie?iace N oa IP3 ?aoeaioi??a.

Iaoaaio?iiiee iaoai?ci io?eia?a?/ii? eaeueoe??ai? neaiae?caoe?? a
aeine?aeaeoaaieo iae?iiao aeyaeany ia aeoaea aoaeoeaiei — i?e
iine?aeiaieo aie?eaoe?yo AOO a aaceaeueoe??aiio ?ic/ei? a?aeiia?aeia
aeaii oaeaeei aeniaaeoaaeinue. Oe?eaai e oa, ui a iae?iiao 14-aeaiieo
uo??a eioa?i-/ooeeaa aeaii, iaaooue, ia a?ae?a?a? nooo?ai? ?ie? a
iia?e?caoe?? ?ii?a eaeueoe?th i?e i?aeaeuai?e [Ca2+]i.

?acoeueoaoe iaoeo aeine?aeaeaiue /?oei aeacothoue ia oa, ui i?ioyaii 3 ?
4 oeaei?a iinoiaoaeueiiai ?icaeoeo iae?ii?a nainiiioi?ii? ei?e uo??a a
iaoai?ciao eaeueoe??ai? neaiae?caoe?? a?aeaoaathoueny cia/i? ci?ie. Oeae
ia??iae iani?aaae? ? aeoaea e?eoe/iei aeey aeic??aaiiy ee?oei
iaiei?oaeno, oi?ioaaiiy aeaiae?eoiiai aea?aaa ? iae?iiaeueii? ia?aae?
(Miller 1988; Juraska & Fifkova, 1979).

Iaie aoei iieacaii, ui ?niothoue cia/i? ci?ie a aeni?an??
iecueeiii?iaiaeo Ni2+- /ooeeaeo eaiae?a (O-oeio) a i?ioean? ?icaeoeo
ee?oei. Oea aeia?a ni?aa?aeiineoueny c aeaieie, io?eiaieie ?ai?oa
noiniaii a?eiaeo ci?i a aeni?an?? iioaioe?ae-caeaaeieo eaiae?a iae?ii?a
ci?iai? ei?e uo??a (Tarasenko et al., 1998), a oaeiae iae?iiao
eaoa?iaei?naeueiiai yae?a oaeaiono (Dzhura et al., 1996). ?o aeoeaaoe?y
iiaea aooe iaiao?aeiith aeey caioneo eieaeueieo eaeueoe??aeo neaiae?a,
iia’ycaieo c aeni?an??th aai?a, ui a?aeiia?aeathoue ca
aeeoa?aioe?thaaiiy oa c?inoaiiy a?ae?inoe?a; aiie oaeiae iiaeooue aooe
caeo/ai? a i?ioean aaia?aoe?? neio?ii?ciaaieo inoeeeyoe?e [Ca2+]i,
oa?aeoa?ieo aeey ?aiiueiai ia??iaeo iinoiaoaeueiiai ?icaeoeo (Gu &
Spitzer, 1995).

?nio? cia/ii iaioa aeaieo i?i aiaeia?/i? a?eia? iaiaaeaiiy a aeni?an??
aioo??oiueiee?oeiieo iaoai?ci?a aea?eueiaiiy eaeueoe?th. ?ai?oa a
a?aioey?ieo iae?iiao iici/eo ieoae aoei iieacaii, ui IP3-?iaeoeiaaia
aea?eueiaiiy Na2+ iiaea a?aeaoaaoenue i?e aeoeaaoe?? iaoaaio?iiieo
aeooaiaoieo ?aoeaioi??a o?eueee ia ?aii?e noaae?? iinoiaoaeueiiai
iioiaaiaco (6 aei?a). I?ci?oa (30 aei?a) oeae iaoai?ci iia?e?caoe??
eaeueoe?th iiai?noth cieea? (Kirischuk 1996b). A iae?iiao nainiiioi?ii?
ei?e iaie aoee io?eiai? aiaeia?/i? ?acoeueoaoe, iaeiae, ana ae a 1/3
oanoiaaieo iae?ii?a 30-aeaiieo uo??a ie ?a?no?oaaee aeoeaaoe?th
iaoaaio?iiieo io?eii?aoeaioi??a ? i?aeaeuaiiy [Ca2+]? a aaceaeueoe??aiio
?ic/ei?.

Ine?eueee iaoai?ci IP3-/ooeeaiai aea?eueiaiiy eaeueoe?th a
aeine?aeaeoaaieo iae?iiao aeyaeany aeiaie? neaaeei, iniaeeai a iae?iiao
aei?ineeo uo??a, aeey oiiei? ?aaoeyoe?? [Ca2+]i iaoai?ci NINR i?a ae
aooe iaiao?aeiei. Iaie aoea aeyaeaia a?aenooi?noue eaeueoe??aeo
o?aice?i?a i?e aie?eaoe?? 20 – 40 iI eioa?io a iae?iiao 14-aeaiieo
uo??a. *e iia’ycaii oea c a?aenooi?noth eioa?i-/ooeeaiai aeaii, yeeiinue
eiai ii?oieia?/ieie iniaeeainoyie ia oeueiio aoai? ?icaeoeo ee?oei,
iac?icoi?ei. Aea a 70% aeine?aeaeoaaieo iae?ii?a 30-aeaiieo uo??a
aie?eaoe?y eioa?io aeeeeeaea oaea cia/ia i?aeaeuaiiy [Ca2+]i, i?e/iio a
aaceaeueoe??aiio ?ic/ei? aiie?ooaea a?aeiia?ae? i?aeoe/ii ia
ci?ithaaeanue. Oe? aeai? ciaoiaeyoueny o a?aeiia?aeiino? c ?acoeueoaoaie
?ioiio?i?/ieo aeine?aeaeaiue eieae?caoe?? IP3- ? eioa?i-/ooeeaeo eaiae?a
a iiceo uo??a. Aoei aeyaeaii, ui a iae?iiao iioi?ii? ei?e IP3 ?aoeaioi?e
ciaoiaeyoueny a nii? ? i?ieneiaeueieo aeaiae?eoao ee?oei, a oie /an ye
??aiiae?iia? ?aoeaioi?e ciaoiaeyoueny ia?aaaaeii a aeiaaeo, oiieeo
ai?eaeueieo aeaiae?eoao (Sharp, 1993). A?aenooi?noue eioa?i-?iaeoeiaaii?
a?aeiia?ae? a iae?iiao 14-aeaiieo uo??a i?aeoaa?aeaeo? oa, ui ia oeueiio
aoai? oi?ioaaiiy aeaiae?eoiiai aea?aaa ua ia caaa?oaii, aea a c??eeo
iae?iiao 30-aeaiieo oaa?ei oeae i?ioean cae?i/aii, coi?iiaai aaeeeee
aiaeiieaciaoe/iee ?aoeeoeoi ? eioa?i-/ooeeaa eaeueoe??aa aeaii ia?
cia/io ?ii?noue.

Aeai? iaoeo aenia?eiaio?a na?ae/aoue i?i iaiiaia nionoioaiiy caian?a
eaeueoe?th a aiaeiieaciaoe/iiio ?aoeeoeoi? a iae?iiao 21-aeaiieo uo??a
i?e ia?ao?ani?e aeoeaaoe?? ??aiiaeeiiaeo oa IP3-?aoeaioi??a, ui iiaea
aiai?eoe i?i ?nioaaiiy ??cieo aeaii aeey oeeo aeaio oeyo?a aea?eueiaiiy
eaeueoe?th ?/aai ?o i?inoi?iai? ?cieueiaaiino?. Oe?eaai, ui a
eoeueoeaiaaieo ano?ioeeoao nieiiiai iiceo iaa?oue i?e aeoeaaoe?? ??cieo
oei?a iaoaaio?iiieo io?eii?aoeaioi??a (?2O e ?2U) aea?eueiaiiy
eaeueoe?th a?aeaoaaeiny oaeiae c ??cieo, i?inoi?iai a?aeie?aieaieo
IP3-/ooeeaeo ioe?a (Indestrup & Salter, 1998). A eoeueoeaiaaieo iae?iiao
a?iieaiio ? oaeaiono AOO- ? eioa?i-?iaeoeiaai? eaeueoe??a? o?aice?ioe
aoee iacaeaaeieie, ui na?ae/eei i?i o/anoue 2 ??cieo eaeueoe??aeo aeaii
(Mironov, 1994).

AENIIAEE

1. ?acoeueoaoe aeaiiai aeine?aeaeaiiy iieacaee, ui iioiaaiaoe/iee
?icaeoie iae?ii?a II-III oa??a nainiiioi?ii? ei?e uo??a i?ecaiaeeoue aei
ci?i iaoai?ci?a, ui aa?ooue o/anoue a eaeueoe??a?e neaiae?caoe??.

2. Ca?eueoaiiy aioo??oiueiee?oeiii? eiioeaio?aoe?? ?ii?a eaeueoe?th,
aeeeeeaia eae??aith aeaiiey?ecaoe??th a cacia/aieo iae?iiao
nainiiioi?ii? ei?e, a?aeaoaa?oueny ca ?aooiie aeoeaaoe?? aeae?eueeio
oei?a iioaioe?ae-ea?iaaieo Ca2+ eaiae?a ieaciaeaie, i?e/iio iae?iie
14-aeaiieo uo??a iathoue a?eueoo u?euei?noue iecueeiii?iaiaeo
i?eaeue-/ooeeaeo eaeueoe??aeo eaiae?a i?ae 30-aeaii?.

3. A iae?iiao nainiiioi?ii? ei?e ?nio? io?eia?a?/ia eaeueoe??aa
neaiae?caoe?y, i?e/iio a oi?ioaaii? eaeueoe??aeo o?aice?io?a aa?ooue
o/anoue ye ?iiio?iii?, oae ? iaoaaio?iii? io?eii?aoeaioi?e, aeoeaaoe?y
yeeo aeeeeea? aioo??oiueiee?oeiia aea?eueiaiiy eaeueoe?th. Iaoaaio?iii?
?2O io?eii?aoeaioi?e aeni?anothoueny a on?o iae?iiao 14-aeaiieo uo??a;
a oie /an ye a iae?iiao aei?ineeo uo??a – o?eueee a 1/3
aeine?aeaeoaaieo ee?oei.

4. A ia?aaaaei?e a?eueoino? aeine?aeaeoaaieo iae?ii?a ei?e 14-aeaiieo
uo??a a?aenooi?e iaoai?ci eaeueoe?e-?iaeoeiaaiiai aea?eueiaiiy
eaeueoe?th c eioa?i-/ooeeaiai aeaii, iaeiae, a iae?iiao 30-aeaiieo
oaa?ei oea aeaii aaea a?ae?a?a? cia/io ?ieue o aioo??oiueiee?oeii?e
eaeueoe??a?e neaiae?caoe??.

5. Oaeei /eiii, a ?aiiueiio ia??iae? ?icaeoeo nooo?aee aianie a
oi?ioaaiiy eaeueoe??aeo o?aice?io?a, iaiao?aeieo aeey ?icaeoeo ?
aeeoa?aioe?thaaiiy, aiinyoue iecueeiii?iaia? eaiaee, a oaeiae nenoaia
aioo??oiueiee?oeiiiai aea?eueiaiiy eaeueoe?th, i?aaenoaaeaia
IP3-/ooeeaei aeaii aiaeiieaciaoe/iiai ?aoeeoeoio. Iaoai?ci
eaeueoe?e-?iaeoeiaaiiai aea?eueiaiiy eaeueoe?th iia’ycaiee c ?icaeoeii
aeaiae?eoiiai aea?aaa ?, iaiaaii, ia? cia/aiiy aeey neaiaeueii? ooieoe??
aeic??eeo iae?ii?a.

Ia?ae?e ?ia?o, iioae?eiaaieo ca iaoa??aeaie aeena?oaoe??

1. U.V. Lalo, I.A. Kruglikov, N.V. Voitenko (1997) ATP-induced calcium
signalling in neocortical neurons in slices. Neurophysiology 29(4/5),
370.

2. O.A. Eaei, I.A. Aieoaiei, I.A. Einothe (1998) ?iii- oa
iaoaaio?iiii-?iaeoeiaai? eaeueoe??a? neaiaee a iae?iiao iaiei?oaeno
uo??a. O?c?ieia?/iee aeo?iae 44 (3), 8.

3. U. Lalo, N. Voitenko, P. Kostyuk (1998) Iono- and metabotropically
induced ?urinergic calcium signalling in rat neocortical neurons. Brain
Research 799(2), 285-291;

4. U. Lalo & P. Kostyuk (1998) Developmental changes in purinergic
calcium signalling in rat neocortical neurons. Developmental Brain
Research 111(1), 43-50;

5. Eaei O., Einothe I. (1998) Ciaioaiiy AOO-?iaeoeiaaii? iaoaaio?iiii?
eaeueoe??ai? a?aeiia?ae? a iae?iiao iaiei?oaeno uo??a, aeeeeeaia
nionoioaiiyi eioa?i/ooeeaiai eaeueoe??aiai aeaii.
Iae?ioeceieiaey/Neurophysiology 30 (4/5), 353-356;

6. Einothe I., Eaei O., Einothe I. (1998) Eaeueoe??aa neaiae?caoe?y a
ei?oeeaeueieo oa oaeai?/ieo iae?iiao uo??a ?c noaioicioioeei?iaeoeiaaiei
ae?aaaoii. Iae?ioeceieiaey/Neurophysiology 30 (4/5), 357-360.

Aiioaoe??:

Eaei O.A. Ci?ie iaoai?ci?a io?eia?a?/ii? eaeueoe??ai? neaiae?caoe?? a
iae?iiao nainiiioi?ii? ei?e uo??a a iinoiaoaeueiiio iioiaaiac?.
–?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, 1999.

Aeena?oaoe?th i?enay/aii aeine?aeaeaiith iaoai?ci?a
aioo??oiueiee?oeiii? eaeueoe??ai? neaiae?caoe?? a iae?iiao II-III oa??a
nainiiioi?ii? ei?e uo??a in situ, a oiieeo c??cao iiceo. Aeey
aei??thaaiiy eiioeaio?aoe?? [Ca2+]i aoa aeei?enoaiee ia?iaaceaiee iaoiae
caaaioaaeaiiy iae?ii?a iaia?aiii?iieeiith oi?iith oeoi?anoeaioiiai
aa?aieea Fura-2/AM. Aoee ioa?aeoa?eciaai? iniiai? iaoai?cie aaia?aoe??
eaeueoe??aeo neaiae?a a iae?iiao nainiiioi?ii? ei?e uo??a ??cieo
a?eiaeo a?oi, a oaeiae aia?oa iieacaii ?nioaaiiy ?iii- oa iaoaaio?iiieo
io?eia?a?/ieo iaoai?ci?a caoaeaeaiiy a oeeo iae?iiao. Iienai?
aeanoeaino? ?iiceoieo?eoinoao-/ooeeaeo ? eioa?i-/ooeeaeo eaeueoe??aeo
aeaii. Iieacaii, ui iaoaaio?iii? ?2O io?eii?aoeaioi?e aeni?anothoueny a
on?o iae?iiao 14-aeaiieo uo??a, a oie /an ye a iae?iiao aei?ineeo
uo??a – o?eueee a 30% aeine?aeaeaieo ee?oei. A ia?aaaaei?e a?eueoino?
aeine?aeaeaieo iae?ii?a ei?e 14- aeaiieo uo??a iaoai?ci
eaeueoe?e-?iaeoeiaaiiiai aea?eueiaiiy eaeueoe?th c eioa?i-/ooeeaiai
aeaii a?aenooi?e, iaeiae, a iae?iiao 30-aeaiieo oaa?ei oea aeaii aaea
a?ae?a?a? cia/io ?ieue o aioo??oiueiee?oeii?e eaeueoe??a?e
neaiae?caoe??.

Eeth/ia? neiaa: iaiei?oaen, eaeueoe??a? eaiaee, eaeueoe??a? aeaii,
io?eii?aoeaioi?e, ?iiceoieo?eoinoao-?iaeoeiaaia aea?eueiaiiy eaeueoe?th,
eaeueoe?e-?iaeoeiaaia aea?eueiaiiy eaeueoe?th.

Eaei O.A. Eciaiaiey iaoaieciia io?eiy?ae/aneie eaeueoeeaaie
neaiaeecaoeee a iae?iiao nainiiioi?iie ei?u e?un a iinoiaoaeueiii
iioiaaiaca.– ?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, 1999.

Aeenna?oaoeey iinayuaia enneaaeiaaieth iaoaieciia aioo?eeeaoi/iie
eaeueoeeaaie neaiaeecaoeee a iae?iiao II-III neiaa nainiiioi?iiie ei?u
e?un in situ, a oiieeo n?acao iicaa. Aeey ecia?aiey eiioeaio?aoeee
[Ca2+]i aue eniieueciaai iaeiaaceaiue iaoiae caa?ocee iae?iiia
iaia?aiii?iieoeaaiie oi?iie oeoi?anoeaioiiai e?aneoaey Fura-2/AM. Auee
ioa?aeoa?eciaaiu iniiaiua iaoaieciu aaia?aoeee eaeueoeeaauo neaiaeia a
iae?iiao nainiiioi?iie ei?u e?un ?aciuo aic?anoiuo a?oii (14- e
30-aeiaaiuo), a oaeaea aia?aua iieacaii nouanoaiaaiea eiii – e
iaoaaio?iiiuo io?eiy?ae/aneeo iaoaieciia aicaoaeaeaiey a yoeo iae?iiao.

Aiieeooaeu AOO-eiaeooee?oaiuo eaeueoeeaauo o?aiceaioia auee
aeica-caaeneiuie a aeeaiaciia eiioeaio?aoeee io 5 aei 2000 ieI. I?eieiay
aaee/eio aiieeooaeu eaeueoeeaaiai o?aiceaioa, aucaaiiiai i?eeiaeaieai
2000 ieI AOO, ca aaeeieoeo, caaeneiinoue iiaeao auoue i?aaenoaaeaia a
aeaea neaiieaeaeueiie e?eaie, iienuaaaiie o?aaiaieai [Ca2+]i = [Ca2+]i
max [ATP]/([ EN50+[ATP])m, aaea m=1.06 e EN50= 72 ieM.

Aeey ii?aaeaeaiey oeia io?eiy?ae/aneeo ?aoeaioi?ia, yeni?anne?iaaiiuo a
iae?iiao nainiiioi?iie ei?u e?un, iu ii?aaeaeeee ?yaeu yooaeoeaiinoae
aiaeiaia AOO a eiioeaio?aoeee 100 ieI. Iie auee neaaeothueie: a
iae?iiao 14-aeiaaiuo e?un — ATOgS > AOO = AAeO >> AMO> Aaeaiicei »
a,b-methylene ATO » OOO; a aeey 30-aeiaaiuo — ATOgS > AOO > AAeO
a,b-methylene ATO> Aaeaiicei OOO, AMO. Oaeea ?yaeu yooaeoeaiinoae
iicaieytho i?aaeiieiaeeoue i?aeiouanoaaiiia o/anoea ?2O oeia
io?eii?aoeaioi?ia.

Iieacaii, /oi a oi?ie?iaaiee AOO-eiaeooee?iaaii?ai eaeueoeeaaiai
o?aiceaioa iiaoo i?eieiaoue o/anoea iioaioeeae-oi?aaeyaiua eaeueoeeaaua
eaiaeu. Aeeaae a eaeueoeeaaoth neaiaeecaoeeth ?aciuo oeiia eaiaeia
iiaeao cia/eoaeueii eciaiyoueny a oiaea iioiaaiaca. Iu eniieueciaaee
aeieaoi?u ?acee/iuo oeiia iioaioeeae-oi?aaeyaiuo eaeueoeeaauo eaiaeia
aei e ai a?aiy i?eeiaeaiey aeia?eaeeaaiai ?anoai?a. Ni2+ a
eiioeaio?aoeee 50 ieI (aeieaoi? ieceiii?iaiauo eaeueoeeaauo eaiaeia
O-oeia) oiaiueoae aiieeooaeu [Ca2+]i o?aiceaioia, aucaaiiuo i?eeiaeaieai
50iI ENl, a iae?iiao 14-aeiaaiuo e?un ia 47%8% (n=12), a a iae?iiao
30-aeiaaiuo e?un – oieueei ia 15%6%. A aeeyiea aeieaoi?ia
aunieiii?iaiauo eaiaeia L-oeia aa?aiaieea e ieoaaeeieia auei iaeeiaeiaui
a iaaeo a?oiiao iae?iiia. ?acoeueoaou ynii iieacuaatho nouanoaaiiua
naeaeae a yeni?annee ieceiii?iaiauo eaeueoeeaauo eaiaeia ia i?ioyaeaiee
enneaaeiaaiiiai ia?eiaea ?acaeoey: ieioiinoue ieceiii?iaiauo eaiaeia
oiaiueoaaony.

Aiieeeaoeey AOO a aaneaeueoeeaaii ?anoai?a aucuaaea oaaee/aiea [Ca2+]i
oieueei a 1/3 oanoe?iaaiiuo iae?iiia 30-aeiaaiuo e?un (a 15 ec 46).
Aieaa oiai, enoiuaiea aioo?eeeaoi/iuo aeaii i?ienoiaeeei ai?acaei
auno?aa /ai a iae?iiao 14-aeiaaiuo aeeaioiuo. A aieueoeinoaa neo/aaa
oaea aoi?ay aiieeeaoeey AOO ia aucuaaea eaeueoeeaaiai ioaaoa (a iae?iiao
14-aeiaaiuo e?un eo iiaeii auei iaaethaeaoue i?e 3-4 aiieeeaoeeyo AOO).

Iu aiieeoee?iaaee 100ieI AOO ianeieueei ?ac iiae?yae n eioa?aaeii 60
naeoiae. Aiieeooaeu aoi?iai e iineaaeothueo eaeueoeeaauo ioaaoia (a eo
iiaeii auei ca?aaeno?e?iaaoue aei 10-12 ?ac) auee iaiueoa ia?aie e
ninoaaeyee 70%4% (n=9) ii n?aaiaieth n aaee/eiie aiieeooaeu ia?aiai
AOO-eiaeooee?iaaiiiai [Ca2+]i o?aiceaioa. Oiaiueoaiea aiieeooaeu aoi?iai
e iineaaeothueo ioaaoia iiaeao auoue aucaaii a) aeanaineoecaoeeae
io?eii?aoeaioi?ia e/eee a) eciaiaieai aeeaaea iaoaaio?iiiiai eiiiiiaioa
(enoiuaieai aioo?eeeaoi/iuo caianieeia). *oiau i?iaa?eoue aeaiiua
i?aaeiieiaeaiey, iu eniieueciaaee oio aea i?ioieie yenia?eiaioa, ii a
i?enoonoaee 1ieI oaineaa?aeia. Aiieeooaea o?aoueaai e iineaaeothueo
[Ca2+]i o?aiceaioia a yoeo oneiaeyo inoaaony iinoiyiiie e ninoaaeyao
65%8% io eiio?ieueiie (n=13). I/aaeaeii, /oi eiaiii yoe [Ca2+]i
o?aiceaiou i?aaenoaaeytho niaie /enoi eiiio?iiioth /anoue eaeueoeeaaiai
ioaaoa. I?e iineaaeiaaoaeueiuo i?eeiaeaieyo AOO, ia/eiay n 3-ae
aiieeeaoeee eiiio?iiiay /anoue eaeueoeeaaiai o?aiceaioa ninoaaeyea ieiei
65%, a aeiey iaoaaio?iiiie /anoe oiaiueoaeanue n 63% (ioeaieaay
iaeneiaeueiue aeeaae iaoaaio?iiiuo io?eii?aoeaioi?ia ii aaee/eia
aiieeooaeu ia?aiai eaeueoeeaaiai ioaaoa a aaneaeueoeeaaii ?anoai?a) aei
35%. Yoi oiaiueoaiea iiaeao auoue naycaii n oai, /oi a) aioo?eeeaoi/iua
aeaii ia?acaiieiythony ia iieiinoueth i?e iineaaeiaaoaeueiuo
aiieeeaoeeyo n 60-naeoiaeiui eioa?aaeii e, oaeei ia?acii, oiaiueoaaony
eiee/anoai eiiia Ca2+, niiniaiuo e aunaiaiaeaeaieth i?e aeoeaaoeee
iaoaaio?iiiuo io?eii?aoeaioi?ia; a) aiciiaeii, i?ienoiaeeo
aeanaineoecaoeey ?2O ?aoeaioi?ia; a) iiaeao auoue, nouanoaotho ?acee/ey
a ooieoeeiie?iaaiee iaoaieciia aioo?eeeaoi/iie eaeueoeeaaie iiaeeecaoeee
a ii?iaeueiii e aaneaeueoeeaaii ?anoai?ao e, a neeo yoiai, iaei??aeoii
eniieueciaaoue aaee/eio aiieeooaeu eaeueoeeaaiai o?aiceaioa a
aaneaeueoeeaaii ?anoai?a aeey ioeaiee aeeaaea iaoaaio?iiiuo ?aoeaioi?ia
a iauai ioaaoa a ii?iaeueiii ?anoai?a.

Iiauoaiea o?iaiy [Ca2+]i iiaeao oaeaea aucuaaoue
eaeueoeee-eiaeooee?iaaiiia aunaiaiaeaeaiea eaeueoeey (CICR) ec
eioaei-/oanoaeoaeueiiai aeaii. Iiyoiio i?e enneaaeiaaiee iaoaieciia
io?eiy?ae/aneie eaeueoeeaaie neaiaeecaoeee iaeuecy ia oaeaeeoue aieiaiea
ooieoeeiie?iaaieth eioaei-/oanoaeoaeueiiai aeaii. Ia?aae aiieeeaoeeae
eioaeia iae?iiu auee aeaiiey?eciaaiu i?eeiaeaieai aeia?eaeeaaiai
?anoai?a, /oiau eiathueany aioo?eeeaoi/iua aeaii auee ia?acaiieiaiu
eiiaie eaeueoeey, niiniaiuie e aunaiaiaeaeaieth. Iaeiaei, 10-20
naeoiaeiua aiieeeaoeee eioaeia a eiioeaio?aoeeyo aei 40 iI ia i?eaiaeeee
e oaaee/aieth aioo?eeeaoi/iie eiioeaio?aoeee naiaiaeiiai eaeueoeey a 90%
(23 ec 26)iae?iiia 14-aeiaaiuo e?un, aeaaea i?e iiauoaiiie [Ca2+]i.
Iaeiaei, a 28 ec 42 enneaaeiaaiuo iae?iiia 30-aeiaaiuo e?un 5-10
naeoiaeiay aiieeeaoeey 20 – 40 iI eioaeia aucuaaea cia/eoaeueiue [Ca2+]i
o?aiceaio, i?aeoe/anee ia iaiythueeny a aaneaeueoeeaaii ?anoai?a, ii
en/acathuee a i?enoonoaee 1 ieI oaineaa?aeia. Aue naeaeai auaiae, /oi
iaoaieci eaeueoeee-eiaeooee?iaaiiiai inaiaiaeaeaiey eaeueoeey naycai n
?acaeoeai aeaiae?eoiiai aea?aaa e, ii-aeaeeiiio, eiaao cia/aiea aeey
neaiaeueiie ooieoeee nic?aaoeo iae?iiia.

Eeth/aaua neiaa: iaiei?oaen, eaeueoeeaaua eaiaee, eaeueoeeaaua aeaii,
io?eii?aoeaioi?u, eiiceoieo?eoinoao-eiaeooee?iaaiiia aunaiaiaeaeaiea
eaeueoeey, eaeueoeee-eiaeooee?iaaiiia aunaiaiaeaeaiea eaeueoeey.

Lalo U.V. Changes in mechanisms of purinergic calcium signalling in rat
sensorimotor neurons in postnatal ontogenesis.- Manuscript.

The dissertation is presented in accordance with requirements for the
degree of candidate of biological sciences in speciality 03.00.02 –
biophysics.-Bogomoletz Institute of Physiology, National Academy of
Sciences of Ukraine, Kiev,1999.

Dissertation is devoted to investigation of intracellular calcium
signalling mechanisms in neurons of II-III layers of sensorimotor cortex
in thin brain slices in situ. Neocortical neurones were loaded with
calcium indicator Fura-2/AM. The principal mechanisms of calcium signals
generation were examined for different age group neurons and for the
first time demonstrate the existence of iono – and metabotropic
mechanisms of exiting these neurons. Property of inositoltriphosphate –
and caffeine-sensitive calcium stores were described. It was
demonstrated that metabotropic ?2O purinoreceptors are present in all
neurons of 14-days rats (P14), at the same time only 1/3 of the tested
P30 neurones exhibited responses to applications of ATP in Ca2+- free
solution. No caffeine — induced Ca2+-release has been observed in the
P14 neurons. To the contrary, in neurones of the P30 group caffeine
application induced considerable [Ca2+]i transients and respective
calcium store becomes play an essential role in intracellular calcium
signalling.

Key words: neocortex, calcium cannels, calcium stores, purinoreceptors,
inositoltriphosphate- induced calcium release, calcium-induced calcium
release.

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