NMDA receptor-mediated K+ efflux and neuronal apoptosis

Neuronal death induced by activating N-methyl-D-aspartate (NMDA) receptors has been linked to Ca2+ and Na+ influx through associated channels. Whole-c ell recording from cultured mouse cortical neurons revealed a NMDA-evoked o utward current, INMDA-K, carried by K+ efflux at membrane potentials positi ve to -86 millivolts, Cortical neurons exposed to NMDA in medium containing reduced Na+ and Ca2+ (as found in ischemic brain tissue) Lost substantial intracellular K+ and underwent apoptosis. Both K+ loss and apoptosis were a ttenuated by increasing extracellular K+, even when voltage-gated Ca2+ chan nels were blocked. Thus NMDA receptor-mediated K+ efflux may contribute to neuronal apoptosis after brain ischemia.