Zinc potentiation of the glycine receptor chloride channel is mediated by allosteric pathways

Lynch, JW, Jacques, P, Pierce, KD and Schofield, PR (1998) Zinc potentiation of the glycine receptor chloride channel is mediated by allosteric pathways. Journal of Neurochemistry, 71 5: 2159-2168.

Author Lynch, JW
Jacques, P
Pierce, KD
Schofield, PR
Title Zinc potentiation of the glycine receptor chloride channel is mediated by allosteric pathways
Journal name Journal of Neurochemistry   Check publisher's open access policy
ISSN 0022-3042
Publication date 1998
Sub-type Article (original research)
Volume 71
Issue 5
Start page 2159
End page 2168
Total pages 10
Language eng
Abstract Molecular mechanisms of zinc potentiation were investigated in recombinant human alpha 1 glycine receptors (GlyRs) by whole-cell patch-clamp recording and [H-3]strychnine binding assays. In the wild-type (WT) GlyR, 1 mu M zinc enhanced the apparent binding affinity of the agonists glycine and taurine and reduced their concentrations required for half-maximal activation. Thus, in the WT GlyR, zinc potentiation apparently occurs by enhancing agonist binding. However, analysis of GlyRs incorporating mutations in the membrane-spanning domain M1-M2 and M2-M3 loops, which are both components of the agonist gating mechanism, indicates that most mutations uncoupled zinc potentiation from glycine-gated currents but preserved zinc potentiation of taurine-gated currents. One such mutation in the M2-M3 loop, L274A, abolished the ability of zinc to potentiate taurine binding but did not inhibit zinc potentiation of taurine-gated currents. In this same mutant where taurine acts as a partial agonist, zinc potentiated taurine-gated currents but did not potentiate taurine antagonism of glycine-gated currents, suggesting that zinc interacts selectively with the agonist transduction pathway. The intracellular M246A mutation, which is unlikely to bind zinc, also disrupted zinc potentiation of glycine currents. Thus, zinc potentiation of the GlyR is mediated via allosteric mechanisms that are independent of its effects on agonist binding.
Keyword Biochemistry & Molecular Biology
Ligand-gated Ion Channel
Allosteric Potentiation
Glycine-gated Chloride Channel
Divalent Cation
Nicotinic Acetylcholine-receptors
Functional Expression
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 42 times in Thomson Reuters Web of Science Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 13 Aug 2007, 10:44:23 EST