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

J Physiol. 1995 Mar 15;483 ( Pt 3)(Pt 3):613-9. doi: 10.1113/jphysiol.1995.sp020610.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chimera
  • Electric Conductivity
  • Electrophysiology
  • Extracellular Space / metabolism
  • Glycine / metabolism
  • Glycine / pharmacology
  • Humans
  • Ions
  • Molecular Sequence Data
  • Neurons / drug effects
  • Neurons / physiology
  • Oocytes / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Glycine / drug effects*
  • Receptors, Glycine / genetics
  • Receptors, Glycine / physiology
  • Recombinant Proteins
  • Spinal Cord / cytology
  • Xenopus
  • Zinc / metabolism
  • Zinc / pharmacology*


  • Ions
  • Receptors, Glycine
  • Recombinant Proteins
  • Zinc
  • Glycine