Cellular neuroscienceModulation of inhibitory glycine receptors in cultured embryonic mouse hippocampal neurons by zinc, thiol containing redox agents and carnosine
Section snippets
Embryonic mouse hippocampal cultures
Animal care and experimental protocols complied with all applicable federal laws and regulations of the United States, and they were approved by the Animal Studies Committee of Washington University. All efforts were made to minimize the number of animals used and their suffering. Hippocampal neurons were cultured from Swiss Webster mouse embryos at day 16 of gestation as described previously (Thio et al 2003, Karkar et al 2004). Briefly, cells were obtained by enzymatically digesting
Zn2+ biphasically modulates glycine currents mediated by α2-containing GlyRs
Glycine, β-alanine, and taurine evoke dose-dependent, strychnine sensitive, chloride currents mediated by α2-containing GlyRs in cultured embryonic mouse hippocampal neurons (Thio et al 2003, Karkar et al 2004). We and others showed that GlyRs in this preparation lack α1 subunits but contain α2 subunits with α2β heteromers predominating over α2 homomers (Thio et al 2003, Mangin et al 2005).
Zn2+ biphasically modulated glycine currents mediated by α2-containing GlyRs. Zn2+ reversibly potentiated
Discussion
This study examined modulation of hippocampal GlyRs by Zn2+ and redox agents as well as the interaction between them. The findings demonstrate that Zn2+ is a potent and effective biphasic modulator of α2-containing GlyRs, though the mechanism of modulation is agonist dependent. While these receptors are relatively resistant to redox modulation, thiol containing redox agents and carnosine can prevent Zn2+ from modulating GlyRs by chelation.
Acknowledgments
This work was supported by NIH grant K02NS043278 and the Department of Neurology, Washington University School of Medicine. We thank Nicholas Rensing for preparing and maintaining the neuronal cultures, Kelvin Yamada for helpful discussions, and Edwin Trevathan for statistical advice.
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