Sodium influx plays a major role in the membrane depolarization induced byoxygen and glucose deprivation in rat striatal spiny neurons

Background and Purpose-Striatal spiny neurons are selectively vulnerable to ischemia, but the ionic mechanisms underlying this selective vulnerability are unclear, Although a possible involvement of sodium and calcium ions ha s been postulated in the ischemia-induced damage of rat striatal neurons, t he ischemia-induced ionic changes have never been analyzed in this neuronal subtype. Methods-We studied the effects of in vitro ischemia (oxygen and glucose dep rivation) at the cellular level using intracellular recordings and microflu orometric measurements in a slice preparation. We also used various channel blockers and pharmacological compounds to characterize the ischemia-induce d ionic conductances. Results-Spiny neurons responded to ischemia with a membrane depolarization/ inward current that reversed at approximately -40 mV. This event was couple d with an increased membrane conductance. The simultaneous analysis of memb rane potential changes and of variations in [Na+](i) and [Ca2+](i) levels s howed that the ischemia-induced membrane depolarization was associated with an increase of [Na+](i) and [Ca2+](i). The ischemia-induced membrane depol arization was not affected by tetrodotoxin or by glutamate receptor antagon ists. Neither intracellular BAPTA, a Ca2+ chelator, nor incubation of the s lices in low-Ca2+-containing solutions affected the ischemia-induced depola rization, whereas it was reduced by lowering the external Nai concentration . High doses of blockers of ATP-dependent K+ channels increased the membran e depolarization observed in spiny neurons during ischemia. Conclusions-Our findings show that, although the ischemia-induced membrane depolarization is coupled with a rise of [Na+](i) and [Ca2+](i), only the N a+ influx plays a prominent role in this early electrophysiological event, whereas the increase of [Ca2+](i) might be relevant for the delayed neurona l death. We also suggest that the activation of ATP-dependent K+ channels m ight counteract the ischemia-induced membrane depolarization.