NMDA receptor-mediated K+ efflux and neuronal apoptosis

Science. 1999 Apr 9;284(5412):336-9. doi: 10.1126/science.284.5412.336.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Channels / metabolism
  • Cells, Cultured
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / metabolism
  • Culture Techniques
  • Glutamic Acid / metabolism
  • Ion Channel Gating
  • Ion Transport
  • Membrane Potentials
  • Mice
  • N-Methylaspartate / pharmacology
  • Neocortex / cytology
  • Neocortex / embryology
  • Neocortex / metabolism
  • Neurons / cytology*
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Potassium / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Sodium / metabolism
  • Sodium / pharmacology

Substances

  • Calcium Channels
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • N-Methylaspartate
  • Sodium
  • Potassium
  • Calcium