Abstract
Glycine receptors (GlyRs), together with GABAA and nicotinic acetylcholine (ACh) receptors, form part of the ligand-activated ion channel superfamily and regulate the excitability of the mammalian brain stem and spinal cord. Here we report that the ability of the neurotransmitter glycine to gate recombinant and native ionotropic GlyRs is modulated by the G protein βγ dimer (Gβγ). We found that the amplitude of the glycine-activated Cl− current was enhanced after application of purified Gβγ or after activation of a G protein–coupled receptor. Overexpression of three distinct G protein α subunits (Gα), as well as the Gβγ scavenger peptide ct-GRK2, significantly blunted the effect of G protein activation. Single-channel recordings from isolated membrane patches showed that Gβγ increased the GlyR open probability (nPo). Our results indicate that this interaction of Gβγ with GlyRs regulates both motor and sensory functions in the central nervous system.
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Acknowledgements
We thank S.R. Ikeda and N.L. Harrison for the plasmids, S.R. Ikeda for critically reading the manuscript, and L.J. Aguayo, A. Ghazanfari and J.T. Healey for technical assistance. This work was supported by Fondecyt, GIA-DIUC (L.G.A. and J.O.), and by the National Institute on Alcohol Abuse and Alcoholism intramural program (R.W.P.).
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Yevenes, G., Peoples, R., Tapia, J. et al. Modulation of glycine-activated ion channel function by G-protein βγ subunits. Nat Neurosci 6, 819–824 (2003). https://doi.org/10.1038/nn1095
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DOI: https://doi.org/10.1038/nn1095
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