Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel.
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.
Wickman
K D
KD
Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905.
Iñiguez-Lluhl
J A
JA
Davenport
P A
PA
Taussig
R
R
Krapivinsky
G B
GB
Linder
M E
ME
Gilman
A G
AG
Clapham
D E
DE
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002793:Cholic Acids; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D015640:Ion Channel Gating; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism
D002793:Cholic Acids; D015221:Potassium Channels; D011994:Recombinant Proteins; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins; D000109:Acetylcholine; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate