NMDA Receptor-Mediated K+ Efflux and Neuronal Apoptosis

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Science  09 Apr 1999:
Vol. 284, Issue 5412, pp. 336-339
DOI: 10.1126/science.284.5412.336

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Neuronal death induced by activatingN-methyl-d-aspartate (NMDA) receptors has been linked to Ca2+ and Na+ influx through associated channels. Whole-cell recording from cultured mouse cortical neurons revealed a NMDA-evoked outward current,I NMDA-K, carried by K+ efflux at membrane potentials positive 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 attenuated by increasing extracellular K+, even when voltage-gated Ca2+channels were blocked. Thus NMDA receptor–mediated K+efflux may contribute to neuronal apoptosis after brain ischemia.

  • * These authors contributed equally to this work.

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