Modulation by zinc ions of native rat and recombinant human inhibitory glycine receptors.
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.
Laube
B
B
Department of Neurochemistry, Max Planck Institute for Brain Research, Frankfurt, Germany.
Kuhse
J
J
Rundström
N
N
Kirsch
J
J
Schmieden
V
V
Betz
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002678:Chimera; D004553:Electric Conductivity; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007477:Ions; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins; D013116:Spinal Cord / Q000166:cytology; D014981:Xenopus; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
D007477:Ions; D018009:Receptors, Glycine; D011994:Recombinant Proteins; D015032:Zinc; D005998:Glycine