Modulation by zinc ions of native rat and recombinant human inhibitory glycine receptors.

Abstract

1. The effect of the divalent cation Zn2+ on inhibitory glycine receptor (GlyR) currents was investigated in rat embryonic spinal cord neurons and Xenopus oocytes expressing recombinant GlyRs. 2. In cultured spinal neurons, Zn2+ potentiated glycine‐induced whole‐cell currents about 3‐fold when applied extracellularly at concentrations of 0.5‐10 microM. In contrast, higher concentrations (> 100 microM) of Zn2+ decreased the glycine response. 3. A similar biphasic modulation of glycine‐induced currents by Zn2+ was also found with recombinant homo‐ and hetero‐oligomeric GlyRs generated in Xenopus oocytes. Dose‐response analysis showed that both the potentiating and inhibitory effects of Zn2+ result from changes in apparent agonist affinity. 4. Analysis of chimeric constructs of the GlyR alpha 1‐ and beta‐subunits revealed that the positive and negative modulatory effects of Zn2+ are mediated by different regions of the alpha 1‐subunit. 5. Our data indicate the existence of distinct high‐ and low‐affinity Zn2+ binding sites on the ligand‐binding alpha‐subunits of the GlyR. These sites may be implicated in the regulation of synaptic efficacy within glycinergic pathways.