医学神经生物学：缺血性神经元损伤及其修复.pptVIP

h*胞外Ca2＋浓度远远高于胞内，因此维持胞内低Ca2＋水平极为重要。*Ca2＋的外排机制有二：Ca2＋-ATP酶和Na+／Ca2＋交换体。缺血时能量储备的耗竭严重影响了Ca2＋的外排．Na+／Ca2＋交换体的作用甚至翻转，将Ca2＋泵入细胞。Ca2＋进入细胞的机制则主要通过电压依赖性和递质门控性Ca2＋通道。缺血导致细胞膜去极化，电压依赖性Ca2＋通道开放；而缺血时突触间隙大量的谷氨酸则激活了递质门控性Ca2＋通道—一NMDA受体。这样，缺血使得细胞内[Ca2＋]升高。此外，突触间隙的谷氨酸还激活了Gq蛋白偶联的代谢型谷氨酸受体，该受体的激活使第二信使1，4，5-三磷酸肌醇(1P3)生成增加。内质网上具有IP3敏感的钙池，IP3的增加也导致内质网内储存的Ca2＋释放，进一步增加了细胞内游离Ca2＋浓度。Ca2+外排：Na+-Ca2+交换体离子梯度丧失，功能翻转Ca2+-ATPase能量耗竭Ca2+内流：电压依赖性Ca2+通道细胞膜去极化，通道开放NMDA受体激活，通道开放*Ca2+homeostasisinneurons.1,Ca2+isremovedfromthecytoplasmbyCa2+-Na+exchangersandadenosinetriphosphate-dependentpumps.2,Ca2+isbufferedbyintracellularanions。3，Subsequentlyitissequesteredinorganelles,suchasmitochondriaandendoplasmicreticulum,inanATP-dependentfashion.Duringischemia,Ca2+pumpsfailbecauseofthelackofATP.4,DecreasesinmembranepotentialleadtoCa2+entrythroughvoltage-dependentCa2+channels.ReleaseofglutamatebyneighboringcellspermitsCa2+entrythroughNMDAandotherCa2+-conductingglutamatereceptors5,andactivatesGq-coulpedmetabotropicglutamatereceptors,6,whichincreasetheformationofinositoltriphosphate(IP3)andthereleaseofCa2+frominternalstores.*Ion-selectivemicropipette(ISM)recordingsystemandbasicneuronalcircuitofcerebellum.Double-barrelledmicropipettescontainionexchangersforCa2+orK+inthetips.ISMsaregluedtogetherwithinter-tipspacingof50umorless.Outputpotentialsarebufferedwithultra-highimpedancebufferamplifiers(1X)andthereferencesignalissubtractedfromtheion-exchangerbarrelsignaltoyieldthetrueionsignal.Toevokeionicchanges,thecerebellarsurfacewasstimulatedwithalocalsurfaceelectrode(Loc),whichexcitedabeamofparallelfibers(axonsofgranulecells)andsynapticallyactivatedPurkinjecelldendrites.Ionchangesandslowpotentialsduringterminalanoxia.Anoxiafollowscirculatoryarrestinducedbyoverdoseofpentobarbital(arrow).Not