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

The data indicate the existence of distinct high‐ and low‐affinity Zn2+ binding sites on the ligand‐binding alpha‐subunits of the GlyR, which may be implicated in the regulation of synaptic efficacy within glycinergic pathways.

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.