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Journal of Neuroscience, Vol 10, 108-116, Copyright © 1990 by Society for Neuroscience
Effect of zinc on NMDA receptor-mediated channel currents in cortical neurons
CW Christine and DW Choi
Department of Neurology, Stanford University Medical Center, California 94305.
Recent data have indicated that the divalent cation Zn2+ can selectively
block central neuronal excitation mediated by N-methyl-D- aspartate (NMDA)
receptors. The present experiments were conducted to determine the action
of Zn2+ at the single-channel level. Outside-out membrane patches were
prepared from cultured murine cortical neurons. Glutamate, 3 microM, in the
presence of 5 microM glycine activated channels with a main conductance
state of about 50 pS which were blocked in a voltage-dependent manner by
Mg2+. Zn2+ appeared to have 2 effects on these NMDA receptor-activated
channels. First, at concentrations as low as 1-10 microM, Zn2+ produced a
concentration- dependent reduction in channel open probability, insensitive
to membrane voltage between -60 and +40 mV; about 50% reduction in open
probability was produced by 3 microM Zn2+. This reduction was mostly due to
a decrease in opening frequency and only weakly mimicked by Mg2+. Second,
at higher concentrations (10-100 microM) and negative membrane voltages,
Zn2+ additionally produced an apparent reduction in single-channel
amplitude, associated with an increase in channel noise, suggestive of a
fast channel block. The amplitude reduction was voltage- dependent, with a
delta of 0.51; amplitude distribution analysis suggested that this voltage
dependence was primarily contributed by the "on" blocking rate constant,
with little contribution from the "off" rate constant. The channel block
produced by Zn2+ was faster than that of Mg2+, which at 100 microM and
negative membrane voltages induces flickering of the NMDA
receptor-activated channel without changing apparent channel
amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)
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