Slow voltage-dependent changes in channel open-state probability underlie hysteresis of NMDA responses in Mg(2+)-free solutions

Neuron. 1992 Jan;8(1):181-7. doi: 10.1016/0896-6273(92)90119-x.


Many single-channel studies rely on the assumption that the channels are functioning under steady-state conditions. In examining the basis for nonlinear whole-cell current-voltage curves in Mg(2+)-free solutions we discovered that N-methyl-D-aspartate (NMDA) channels in excised patches reversibly shifted their open-state probability (Po) in a voltage-dependent way, exhibiting approximately 3- to 4-fold greater Po at positive potentials than at rest. Changes in Po were mainly attributable to shifts in frequency of channel opening. Po changed remarkably slowly (2-15 min), explaining the hysteresis of whole-cell current-voltage curves obtained in nonequilibrium conditions. The slow increase in Po provides a mechanism by which NMDA channels can substantially increase Ca2+ influx in cells depolarized for prolonged periods of time and may play a role in excitotoxicity.

Publication types

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

MeSH terms

  • Animals
  • Dithiothreitol / pharmacology
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Ion Channels / drug effects
  • Ion Channels / physiology*
  • Kinetics
  • Magnesium / pharmacology
  • Membrane Potentials
  • Mice
  • N-Methylaspartate / metabolism
  • N-Methylaspartate / pharmacology*
  • Probability
  • Receptors, N-Methyl-D-Aspartate / physiology*


  • Ion Channels
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • Magnesium
  • Dithiothreitol