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Science 9 April 1999:
Vol. 284. no. 5412, pp. 336 - 339
DOI: 10.1126/science.284.5412.336

Reports

NMDA Receptor-Mediated K+ Efflux and Neuronal Apoptosis

S. P. Yu, * C.-H. Yeh, * U. Strasser, M. Tian, D. W. Choi dagger

Neuronal death induced by activating N-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, INMDA-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.

Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: choid{at}neuro.wustl.edu


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