Ionic mechanisms underlying differential vulnerability to ischemia in striatal neurons

Brain cells express extremely different sensitivity to ischemic insults. Th e reason for this differential vulnerability is still largely unknown. Here we discuss the ionic bases underlying the physiological responses to in vi tro ischemia in two neostriatal neuronal subtypes exhibiting respectively h igh sensitivity and high resistance to energy deprivation. Vulnerable neost riatal neurons respond to ischemia with a membrane depolarization. This mem brane depolarization mainly depends on the increased permeability to Na+ io ns. In contrast, resistant neostriatal neurons respond to ischemia with a m embrane hyperpolarization due to the opening of K+ channels. Interestingly, in both neuronal subtypes the ischemia-dependent membrane potential change s can be significantly enhanced or attenuated by a variety of pharmacologic al agents interfering with intracellular Ca2+ entry, ATP-dependent K+ chann els opening, and Na+/Ca2+ exchanger functioning. The understanding of the i onic mechanisms underlying the differential membrane responses to ischemia represents the basis for the development of rational neuroprotective treatm ents during acute cerebrovascular insults. (C) 2001 Elsevier Science Ltd. A ll rights reserved.