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

Authors: K D Wickman, J A Iñiguez-Lluhl, P A Davenport, R Taussig, G B Krapivinsky, M E Linder, A G Gilman, D E Clapham

Journal, date & volume: Nature, 1994 Mar 17 , 368, 255-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/8145826

Abstract
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.