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The Journal of Neurophysiology Vol. 85 No. 2 February 2001, pp. 912-925
Copyright ©2001 by the American Physiological Society
1Institut des Neurosciences, Université Pierre et Marie Curie, 75252 Paris Cedex 05; 2Institut National de la Santé et de la Recherche Médicale U 497, Ecole Normale Superieure, 75005 Paris, France; and 3Center for Research in Neuroscience, McGill University, and Montreal General Hospital Research Institute, Montreal, Quebec H3G 1A4, Canada
Suwa, Hiroshi,
Louis Saint-Amant,
Antoine Triller,
Pierre Drapeau, and
Pascal Legendre.
High-Affinity Zinc Potentiation of Inhibitory Postsynaptic
Glycinergic Currents in the Zebrafish Hindbrain. J. Neurophysiol. 85: 912-925, 2001. Zinc has been reported to
potentiate glycine receptors (GlyR), but the physiological significance
of this observation has been put in doubt by the relatively high values
of the EC50, 0.5-1 µM, since such
concentrations may not be attained in the synaptic cleft of glycinergic
synapses. We have re-evaluated this observation in the frame of the
hypothesis that contaminant heavy metals present in usual solutions may
have lead to underestimate the affinity of the zinc binding site, and
therefore to underestimate the potential physiological role of zinc.
Using chelators either to complex heavy metals or to apply zinc at
controlled concentrations, we have examined the action of zinc on GlyR
kinetics in outside-out patches from 50-h-old zebrafish Mauthner cells.
Chelating contaminating heavy metals with tricine or
N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN)
decreased the duration of the currents evoked by glycine, confirming
that traces of heavy metals alter the GlyR response in control
conditions. Using tricine- (10 mM) buffered zinc solution, we then
showed that zinc increases the amplitude of outside-out responses
evoked by 0.1-0.5 mM glycine with an EC50 of 15 nM. In contrast zinc had no effect on the amplitude of currents evoked by a saturating concentration (3-10 mM) of glycine. This suggests that
zinc enhances GlyR apparent affinity for glycine. The study of the
effects of zinc on the kinetics of the response indicates that this
increase of apparent affinity is due to a decrease of the glycine
dissociation rate constant. We then analyzed the effects of zinc on
postsynaptic GlyRs in whole cell recordings of glycinergic miniature
inhibitory postsynaptic currents (mIPSCs). Chelation of contaminant
heavy metals decreased the amplitude and the duration of the mIPSCs;
inverse effects were observed by adding zinc in buffered solutions
containing nanomolar free zinc concentrations. Zinc plus tricine or
tricine alone did not change the coefficient of variation (
0.85) of
the mIPSC amplitude distributions. These results suggest that
postsynaptic GlyRs are not saturated after the release of one vesicle.
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