Journal of Neurophysiology

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Suppression by Zinc of AMPA Receptor-Mediated Synaptic Transmission in the Retina

Dao-Qi Zhang, Christophe Ribelayga, Stuart C. Mangel, Douglas G. McMahon


Zinc is strikingly co-localized with glutamate-containing vesicles in the synaptic terminals of retinal photoreceptors, and it is thought to be co-released with glutamate onto postsynaptic neurons such as horizontal cells and bipolar cells. Here we examined exogenous zinc modulation of glutamate receptors on cultured retinal horizontal cells using patch-clamp recording and endogenous zinc effect on intact horizontal cells using intracellular recording techniques. Application of 3, 30, and 300 μM zinc reduced the whole cell peak current of response to 200 μM glutamate by 2, 30, and 56%, respectively. Zinc suppression of glutamate response persisted in the presence of 10 μM cyclothiazide (CTZ). Glutamate responses of outside-out patches were completely abolished by 30 μM 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), and the receptor desensitization was blocked by 30 μM CTZ, indicating that receptor target for the zinc action on horizontal cells is α-amino-3-hydroxy-5-methyl-4-isoxazoleproponic acid (AMPA) receptors. Zinc decreased the amplitude of outside-out patch peak current without an effect on either its 10–90% rise time or the rate of receptor desensitization. Dose-response curves for glutamate show that zinc reduced the maximal current evoked by glutamate and increased EC50 from 50 ± 3 to 70 ± 6 μM without changing the Hill coefficient. Chelation of endogenous zinc with 1 mM Ca-EDTA depolarized horizontal cells in the intact retina by 3 mV, consistent with relief of the partial glutamate receptor inhibition by zinc. Overall, the results describe a unimodal form of zinc modulation of AMPA-type glutamate receptor responses not previously described in native neuronal preparations and a novel role for endogenous zinc in modulating neurotransmission.


  • Address for reprint requests: D. G. McMahon, Dept. of Biological Sciences, Vanderbilt University, Nashville, TN 37235-1634. (E-mail: dgmcma1{at}

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