The action of N-methyl-D-aspartic acid on mouse spinal neurones in culture

J Physiol. 1985 Apr;361:65-90. doi: 10.1113/jphysiol.1985.sp015633.

Abstract

Neurones from the ventral half of mouse embryo spinal cord were grown in dissociated culture and voltage clamped. The current-voltage relation of responses evoked by N-methyl-D-aspartic acid (NMDA), L-glutamic acid and kainic acid was recorded in media of different ionic composition. On removal of Mg2+ from the extracellular solution, responses to NMDA and L-glutamate became less voltage sensitive, such that NMDA responses were no longer associated with a region of negative slope conductance. The antagonism of NMDA responses produced by application of Mg2+ to neurones bathed in nominally Mg2+-free solutions shows voltage dependence and uncompetitive kinetics. Voltage-jump experiments showed that the voltage-dependent action of Mg2+ occurred rapidly, and with complex kinetics. Ni2+ and Cd2+, two potent blockers of calcium currents in spinal cord neurones, had significantly different potencies as NMDA antagonists, Ni2+ being of greater potency than Mg2+, and Cd2+ considerably weaker. The voltage-dependent block of NMDA responses produced by physiological concentrations of Mg2+ is sufficient to explain the apparent increase in membrane resistance produced by NMDA in current-clamp experiments, and the ability of NMDA to support repetitive firing. Substitution of choline for Na+ produced a hyperpolarizing shift in the reversal potential for responses evoked by kainic acid consistent with an increase in permeability to Na+ and K+. In choline-substituted solutions, the reversal potential of NMDA responses was more positive than that recorded for kainic acid, and in addition NMDA responses showed enhanced desensitization.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / antagonists & inhibitors
  • Aspartic Acid / pharmacology
  • Cells, Cultured
  • Glutamates / pharmacology
  • Glutamic Acid
  • Ion Channels / drug effects
  • Kainic Acid / pharmacology
  • Magnesium / pharmacology
  • Membrane Potentials / drug effects
  • Mice
  • N-Methylaspartate
  • Neurons / drug effects*
  • Spinal Cord / cytology*
  • Time Factors

Substances

  • Glutamates
  • Ion Channels
  • Aspartic Acid
  • Glutamic Acid
  • N-Methylaspartate
  • Magnesium
  • Kainic Acid