A regulator of G protein signalling (RGS) protein confers agonist-dependent relaxation gating to a G protein-gated K+ channel

Abstract

1. The effects of RGS4 on the voltage-dependent relaxation of G protein-gated K+ (K(G)) 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 K(G) 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 K(G) channel subunits. 5. Since the native cardiac K(G) channel exhibited similar agonist-dependent relaxation kinetics to that mediated by RGS4, it is suggested that K(G) channel gating is a novel physiological target of RGS protein-mediated regulation.