ION-CHANNEL INVOLVEMENT IN ANOXIC DEPOLARIZATION-INDUCED BY CARDIAC-ARREST IN RAT-BRAIN

Anoxic depolarization (AD) and failure of ion homeostasis play an impo rtant role in ischemia-induced neuronal injury. In the present study, different drugs with known ion-channel-modulating properties were exam ined for their ability to interfere with cardiac-arrest-elicited AD an d with the changes in the extracellular ion activity in rat brain. Our results indicate that only drugs primarily blocking membrane Na+ perm eability (NBQX, R56865, and flunarizine) delayed the occurrence of AD, while compounds affecting cellular Ca2+ load (MK-801 and nimodipine) did not influence the latency time. The ischemia-induced [Na+](e) redu ction was attenuated by R56865. Blockade of the ATP-sensitive K+ chann els with glibenclamide reduced the [K+](e) increase upon ischemia, ind icating an involvement of the K-ATP channels in ischemia-induced K+ ef flux. The K-ATP channel opener cromakalim did not affect the AD or the [K+](e) concentration. The ischemia-induced rapid decline of extracel lular calcium was attenuated by receptor-operated Ca2+ channel blocker s MK-801 and NBQX, but not by the voltage-operated Ca2+ channel blocke r nimodipine, R56865, and flunarizine.