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-gat ed K+ (K-G) channels were examined by heterologous expression in Xenopus oo cytes. 2. While the relaxation kinetics was unaffected by the acetylcholine concen tration ([ACh]) in the absence of ROS4, it became dependent on [ACh] when R GS4 was co-expressed. 3. Kinetic analyses indicated that RGS4 confers to the K-G channel a voltag e-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 cha nnel gating is a novel physiological target of RGS protein-mediated regulat ion.