The action of N-methyl-D-aspartic acid on mouse spinal neurones in culture.
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.
Mayer
M L
ML
Westbrook
G L
GL
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007473:Ion Channels / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology*; D013997:Time Factors
D005971:Glutamates; D007473:Ion Channels; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D008274:Magnesium; D007608:Kainic Acid