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-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.
Yu
S P
SP
Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Yeh
C
C
Strasser
U
U
Tian
M
M
Choi
D W
DW
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D046508:Culture Techniques; D018698:Glutamic Acid / Q000378:metabolism; D015640:Ion Channel Gating; D017136:Ion Transport; D008564:Membrane Potentials; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology
D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D012964:Sodium; D011188:Potassium; D002118:Calcium