Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published April 18, 1996 | public
Journal Article

Inhibition of an inwardly rectifying K^+ channel by G-protein ɑ-subunits

Abstract

CHOLINERGIC muscarinic, serotonergic, opioid and several other G-protein-coupled neurotransmitter receptors activate inwardly rectifying K^+ channels of the GIRK family, slowing the heartbeat and decreasing the excitability of neuronal cells. Inhibitory modulation of GIRKs by G-protein-coupled receptors may have important implications in cardiac and brain physiology. Previously G_α and G_(βγ) subunits of heterotrimeric G proteins have both been implicated in channel opening, but recent studies attribute this role primarily to the G_(βγ) dimer that activates GIRKs in a membrane-delimited fashion, probably by direct binding to the channel protein. We report here that free GTPγS-activated G_(αil), but not G_(αi2) or G_(αi3), potently inhibits G_(β1γ2)-induced GIRK activity in excised membrane patches of Xenopus oocytes expressing GIRK1. High-affinity but partial inhibition is produced by G_(αs)-GTPγS. G_(αil)-GTPγS also inhibits G_(βlγ2)-activated GIRK in atrial myocytes. Antagonistic interactions between G_α and G_(βγ) may be among the mechanisms determining specificity of G protein coupling to GIRKs.

Additional Information

© 1996 Nature Publishing Group. Received 18 October 1995; accepted 5 February 1996. We thank E. Peralta and J. P. Adelman for the cDNAs of m2 receptor and rcKATP (Kir3.4), respectively, B. Posner for providing G1i;-c685, and M. Malca for oocyte injections. Antisense ODNs to Xenopus G proteins were prepared by W. S. Marshall and co-workers of Amgen Boulder Inc. This work was supported by the Human Frontiers Scientific Program, Israel-USA Binational Science Foundation, Austrian National Bank, Spezialforschungbereich: Biomembranes and Atherosklerosis (Austria), National Institutes of Health, National Institute of General Medical Sciences, and the National Institute of Mental Health.

Additional details

Created:
August 20, 2023
Modified:
October 23, 2023