Sodium influx plays a major role in the membrane depolarization induced by oxygen 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 has been postulated in the ischemia-induced damage of rat striatal neurons, the ischemia-induced ionic changes have never been analyzed in this neuronal subtype. Methods - We studied the effects of in vitro ischemia (oxygen and glucose deprivation) at the cellular level using intracellular recordings and microfluorometric measurements in a slice preparation. We also used various channel blockers and pharmacological compounds to characterize the ischemia-induced ionic conductances. Results - Spiny neurons responded to ischemia with a membrane depolarization/inward current that reversed at approximately -40 mV. This event was coupled with an increased membrane conductance. The simultaneous analysis of membrane potential changes and of variations in [Na⁺](i) and [Ca²⁺](i) levels showed that the ischemia-induced membrane depolarization was associated with an increase of [Na⁺](i) and [Ca²⁺](i). The ischemia-induced membrane depolarization was not affected by tetrodotoxin or by glutamate receptor antagonists. Neither intracellular BAPTA, a Ca²⁺ chelator, nor incubation of the slices in low-Ca²⁺-containing solutions affected the ischemia- induced depolarization, whereas it was reduced by lowering the external Na⁺ concentration. High doses of blockers of ATP-dependent K⁺ channels increased the membrane 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 Na⁺ influx plays a prominent role in this early electrophysiological event, whereas the increase of [Ca²⁺](i) might be relevant for the delayed neuronal death. We also suggest that the activation of ATP-dependent K⁺ channels might counteract the ischemia-induced membrane depolarization.