Calcium dependence of rapid astrocyte death induced by transient hypoxia, acidosis, and extracellular ion shifts
Calcium dependence of rapid astrocyte death induced by transient hypoxia, acidosis, and extracellular ion shifts
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作者：
Bondarenko, A;Chesler, M
暴露在低氧、酸性、离子移位的Ringer(头发)中15-40分钟，已被证明在正常介质中再灌流时会导致星形胶质细胞迅速死亡。头发溶液的离子位移包括细胞外K+(例如，[K+](O))的上升和[Na+](O)、[Cl-](O)和[Ca+](O)的下降，这是脑缺血-创伤性损伤的特征。我们研究了毛发损伤的离子基础。毛发暴露后，在0 Ca~(2+)/EGTA培养液中再灌流可完全保护星形胶质细胞。在BAPTA-AM酯中预先孵育细胞也具有保护作用，表明损伤是由再灌流过程中的钙内流触发的。尼莫地平、CNQX、APV和TTX均未减轻损伤。100 mU的Ni2+或100 mU的苯巴胺可阻断星形胶质细胞的死亡，提示参与了Na+-Ca~(2+)交换。KB-R7943优先抑制Na+-Ca~(2+)反向交换，对星形胶质细胞也有保护作用。[K+](O)升高不是星形胶质细胞死亡的必要条件。然而，当[Na+](O)在整个毛发方案中保持在151 mm时，细胞死亡显著减少。我们推测，[Na+](O)的移位有利于细胞内Na+的负载，从而有助于逆转Na+-Ca2+交换。讨论了星形细胞Na+蓄积的可能途径。Glia 34：143-149,2001。(C)2001年Wiley-Liss，Inc.
Exposure to hypoxic, acidic, ion-shifted Ringer (HAIR) for 15-40 min has been shown to cause rapid astrocyte death upon reperfusion with normal media. The ion shifts of the HAIR solution included a rise in extracellular K+ (e.g., [K+](o)) and a fall in [Na+](o), [Cl-](o), and [Ca2+](o), characteristic of ischemic-traumatic brain insults. We investigated the ionic basis of the HAIR-induced injury. After HAIR exposure, reperfusion in 0 Ca2+/EGTA media completely protected astrocytes. Preincubation of cells in BAPTA-AM ester was also protective, indicating that the injury was triggered by Ca2+ influx during reperfusion. Neither nimodipine, CNQX, APV, nor TTX reduced injury. Astrocyte death could be blocked by 100 muM Ni2+ or 100 muM benzamil, suggesting involvement of Na+-Ca2+ exchange. KB-R7943, which preferentially inhibits reverse Na+-Ca2+ exchange, also protected astrocytes. Elevation of [K+](o) was not necessary for astrocyte death. However, when [Na+](o) was maintained at 151 mM throughout the HAIR protocol, cell death was markedly reduced. We postulate that [Na+](o) shifts aid reversal of Na+-Ca2+ exchange by favoring cytosolic Na+ loading. Possible means of astrocytic Na+ accumulation are discussed. GLIA 34:143-149, 2001. (C) 2001 Wiley-Liss, Inc.