A regulator of G protein signalling (RGS) protein confers agonist-dependent relaxation gating to a G protein-gated K+ channel.
1. The effects of RGS4 on the voltage-dependent relaxation of G protein-gated K+ (KG) channels were examined by heterologous expression in Xenopus oocytes. 2. While the relaxation kinetics was unaffected by the acetylcholine concentration ([ACh]) in the absence of RGS4, it became dependent on [ACh] when RGS4 was co-expressed. 3. Kinetic analyses indicated that RGS4 confers to the KG channel a voltage-independent inhibitory gating mechanism, which was attenuated by ACh in a concentration-dependent fashion. 4. In vitro biochemical studies showed that RGS4 could bind to the protein complex containing KG channel subunits. 5. Since the native cardiac KG channel exhibited similar agonist-dependent relaxation kinetics to that mediated by RGS4, it is suggested that KG channel gating is a novel physiological target of RGS protein-mediated regulation.
Fujita
S
S
Department of Pharmacology II, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Inanobe
A
A
Chachin
M
M
Aizawa
Y
Y
Kurachi
Y
Y
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D020710:RGS Proteins / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014982:Xenopus laevis
D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020710:RGS Proteins; D011994:Recombinant Proteins; C098799:RGS4 protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D000109:Acetylcholine