Modulation of glycine-activated ion channel function by G-protein beta gamma subunits

• Published in: Nature neuroscience Vol. 6; no. 8; pp. 819 - 824
• Main Authors: Yevenes, GE, Peoples, R W, Tapia, J C, Parodi, J, Soto, X, Olate, J, Aguayo, L G
• Format: Journal Article
• Language: English
• Published: 01.08.2003
• ISSN: 1097-6256
• DOI: 10.1038/nn1095

Glycine receptors (GlyRs), together with GABA sub(A) 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 beta gamma dimer (G beta gamma ). We found that the amplitude of the glycine-activated Cl super(-) current was enhanced after application of purified G beta gamma or after activation of a G protein-coupled receptor. Overexpression of three distinct G protein alpha subunits (G alpha ), as well as the G beta gamma scavenger peptide ct-GRK2, significantly blunted the effect of G protein activation. Single-channel recordings from isolated membrane patches showed that G beta gamma increased the GlyR open probability (nP sub(o)). Our results indicate that this interaction of G beta gamma with GlyRs regulates both motor and sensory functions in the central nervous system.