Modulation of glycine-activated ion channel function by G-protein betagamma subunits.
Glycine receptors (GlyRs), together with GABA(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 betagamma dimer (Gbetagamma). We found that the amplitude of the glycine-activated Cl- current was enhanced after application of purified Gbetagamma or after activation of a G protein-coupled receptor. Overexpression of three distinct G protein alpha subunits (Galpha), as well as the Gbetagamma scavenger peptide ct-GRK2, significantly blunted the effect of G protein activation. Single-channel recordings from isolated membrane patches showed that Gbetagamma increased the GlyR open probability (nP(o)). Our results indicate that this interaction of Gbetagamma with GlyRs regulates both motor and sensory functions in the central nervous system.
Yevenes
Gonzalo E
GE
Laboratory of Neurophysiology, Department of Physiology, Box 160-C, University of Concepción, Chile.
Peoples
Robert W
RW
Tapia
Juan C
JC
Parodi
Jorge
J
Soto
Ximena
X
Olate
Juan
J
Aguayo
Luis G
LG
D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000502:physiology; D004553:Electric Conductivity; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D005998:Glycine / Q000494:pharmacology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
D018118:Chloride Channels; D007473:Ion Channels; D010455:Peptides; D018009:Receptors, Glycine; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins; D005998:Glycine