Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits.


Journal Article

Acetylcholine released during parasympathetic stimulation of the vagal nerve slows the heart rate through the activation of muscarinic receptors and subsequent opening of an inwardly rectifying potassium channel. The activation of these muscarinic potassium channels is mediated by a pertussis toxin-sensitive heterotrimeric GTP-binding protein (G protein). It has not been resolved whether exogenously applied G alpha or G beta gamma, or both, activate the channel. Using a heterologous expression system, we have tested the ability of different G protein subunits to activate the cloned muscarinic potassium channel, GIRK1. We report here that coexpression of GIRK1 with G beta gamma but not G alpha beta gamma in Xenopus oocytes results in channel activity that persists in the absence of cytoplasmic GTP. This activity is reduced by fusion proteins of the beta-adrenergic receptor kinase and of recombinant G alpha i-GDP, both of which are known to interact with G beta gamma. Moreover, application of recombinant G beta gamma, but not G alpha i-GTP-gamma S, activates GIRK1 channels. Thus G beta gamma appears to be sufficient for the activation of GIRK1 muscarinic potassium channels.

Full Text

Duke Authors

Cited Authors

  • Reuveny, E; Slesinger, PA; Inglese, J; Morales, JM; Iñiguez-Lluhi, JA; Lefkowitz, RJ; Bourne, HR; Jan, YN; Jan, LY

Published Date

  • July 14, 1994

Published In

Volume / Issue

  • 370 / 6485

Start / End Page

  • 143 - 146

PubMed ID

  • 8022483

Pubmed Central ID

  • 8022483

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/370143a0


  • eng

Conference Location

  • England