Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel.


Journal Article

Acetylcholine activates inwardly rectifying potassium channels (IK.ACh) in the heart through muscarinic receptor binding and activation of pertussis-toxin-sensitive G proteins. Experiments showing that only the beta gamma-subunit (G beta gamma) activates IK.ACh (ref. 4) were challenged by reports that only the activated alpha-subunit (G alpha) was effective. Here we examine IK.ACh regulation using purified brain and recombinant G-protein subunits. Six recombinant G beta gamma-subunits activated IK.ACh with apparent half-maximal activation concentrations of 3-30 nM. Activation of IK.ACh by recombinant G alpha-GTP gamma S was observed, but this was probably due to release of GTP gamma S from the protein. Importantly, IK.ACh activity elicited by GTP gamma S was inhibited by purified brain and recombinant G alpha-GDP, suggesting that native G beta gamma plays a major role in this pathway. We conclude that G beta gamma is a primary regulator of IK.ACh activity.

Full Text

Cited Authors

  • Wickman, KD; Iñiguez-Lluhl, JA; Davenport, PA; Taussig, R; Krapivinsky, GB; Linder, ME; Gilman, AG; Clapham, DE

Published Date

  • March 1994

Published In

Volume / Issue

  • 368 / 6468

Start / End Page

  • 255 - 257

PubMed ID

  • 8145826

Pubmed Central ID

  • 8145826

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/368255a0


  • eng