Na(+) occupancy and Mg(2+) block of the n-methyl-d-aspartate receptor channel.
The effect of extracellular and intracellular Na(+) on the single-channel kinetics of Mg(2+) block was studied in recombinant NR1-NR2B NMDA receptor channels. Na(+) prevents Mg(2+) access to its blocking site by occupying two sites in the external portion of the permeation pathway. The occupancy of these sites by intracellular, but not extracellular, Na(+) is voltage-dependent. In the absence of competing ions, Mg(2+) binds rapidly (>10(8) M(-1)s(-1), with no membrane potential) to a site that is located 0.60 through the electric field from the extracellular surface. Occupancy of one of the external sites by Na(+) may be sufficient to prevent Mg(2+) dissociation from the channel back to the extracellular compartment. With no membrane potential; and in the absence of competing ions, the Mg(2+) dissociation rate constant is >10 times greater than the Mg(2+) permeation rate constant, and the Mg(2+) equilibrium dissociation constant is approximately 12 microM. Physiological concentrations of extracellular Na(+) reduce the Mg(2+) association rate constant approximately 40-fold but, because of the "lock-in" effect, reduce the Mg(2+) equilibrium dissociation constant only approximately 18-fold.
Zhu
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Y
Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Auerbach
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A
D000818:Animals; D004594:Electrophysiology; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry / Q000494:pharmacology*; D008564:Membrane Potentials; D009865:Oocytes; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012964:Sodium / Q000737:chemistry / Q000494:pharmacology*; D013569:Synapses / Q000502:physiology; D014981:Xenopus
D016194:Receptors, N-Methyl-D-Aspartate; D012964:Sodium; D008274:Magnesium