Modulation of inhibitory glycine receptors in cultured embryonic mouse hippocampal neurons by zinc, thiol containing redox agents and carnosine

L. L. Thio, H. X. Zhang

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Modulation of inhibitory glycine receptors by zinc (Zn2+) and endogenous redox agents such as glutathione may alter inhibition in the mammalian brain. Despite the abundance of Zn2+ in the hippocampus and its ability to modulate glycine receptors, few studies have examined Zn2+ modulation of hippocampal glycine receptors. Whether redox agents modulate hippocampal glycine receptors also remains unknown. This study examined Zn2+ and redox modulation of glycine receptor-mediated currents in cultured embryonic mouse hippocampal neurons using whole-cell recordings. Zn2+ concentrations below 10 μM potentiated currents elicited by low glycine, β-alanine, and taurine concentrations by 300-400%. Zn2+ concentrations above 300 μM produced nearly complete inhibition. Potentiating Zn2+ concentrations shifted the dose-response curves for the three agonists to the left and decreased the Hill coefficient for glycine and β-alanine but not taurine. Inhibiting Zn2+ concentrations shifted the dose-response curves for glycine and β-alanine to the right but reduced the maximum taurine response. Histidine residues may participate in potentiation because diethyl pyrocarbonate and pH 5.4 diminished Zn2+ enhancement of glycine currents. pH 5.4 diminished Zn2+ block of glycine currents, but diethyl pyrocarbonate did not. These findings indicate that separate sites mediate Zn2+ potentiation and inhibition. The redox agents glutathione, dithiothreitol, tris(2-carboxyethyl)phosphine, and 5,5′-dithiobis(2-nitrobenzoic acid) did not alter glycine currents by a redox mechanism. However, glutathione and dithiothreitol interfered with the effects of Zn2+ on glycine currents by chelating it. Carnosine had similar effects. Thus, Zn2+ and thiol containing redox agents that chelate Zn2+ modulate hippocampal glycine receptors with the mechanism of Zn2+ modulation being agonist dependent.

Original languageEnglish
Pages (from-to)1315-1327
Number of pages13
JournalNeuroscience
Volume139
Issue number4
DOIs
StatePublished - May 5 2006

Keywords

  • 5,5′-dithiobis(2-nitrobenzoic acid)
  • diethyl pyrocarbonate
  • dithiothreitol
  • glutathione
  • taurine
  • β-alanine

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