Balestrino M
Department of Neurology, University of Genova, Italy.
J Neurosci Methods. 1995 Jun;59(1):99-103. doi: 10.1016/0165-0270(94)00199-q.
Anoxic depolarization has been linked to the generation of hypoxic irreversible damage. Treatments that postpone its occurrence during hypoxia protect against irreversible damage. This work investigates possible mechanisms leading to anoxic depolarization and ways to prevent or delay it. Exogenous creatine (a compound that delays ATP depletion during hypoxia by increasing the intracellular store of phosphocreatine) doubles the latency of anoxic depolarization. Ouabain (100 microM) reproduces in normoxic slices the depolarization of anoxic depolarization and the concurrent changes in [K+]0; thus, failure of (Na+, K+)ATPase (which is likely to occur during hypoxia due to ATP depletion) is sufficient to cause anoxic depolarization. Electrophysiological evidence, however, suggests that failure of this ATPase causes anoxic depolarization through some intermediate event, probably Na(+)-induced cell swelling. In accordance with this hypothesis, increasing extracellular osmolarity with mannitol (25 mM) increases anoxic depolarization latency by approximately 25%. Other possible mechanisms of anoxic depolarization are also discussed.
缺氧去极化与缺氧性不可逆损伤的发生有关。在缺氧期间推迟其发生的治疗方法可预防不可逆损伤。这项工作研究了导致缺氧去极化的可能机制以及预防或延迟它的方法。外源性肌酸（一种通过增加细胞内磷酸肌酸储备来延迟缺氧期间ATP消耗的化合物）使缺氧去极化的潜伏期延长了一倍。哇巴因（100微摩尔）在常氧切片中重现了缺氧去极化的去极化以及细胞外[K+]的同时变化；因此，（Na+，K+）ATP酶的功能衰竭（在缺氧期间由于ATP消耗很可能发生）足以导致缺氧去极化。然而，电生理证据表明，这种ATP酶的功能衰竭通过某种中间事件导致缺氧去极化，可能是Na+诱导的细胞肿胀。根据这一假设，用甘露醇（25毫摩尔）增加细胞外渗透压可使缺氧去极化潜伏期延长约25%。还讨论了缺氧去极化的其他可能机制。
