REGULATORS OF G-PROTEIN SIGNALING (RGS) PROTEINS CONSTITUTIVELY ACTIVATE G-BETA-GAMMA-GATED POTASSIUM CHANNELS

Here we report novel effects of regulators of G protein signaling (RGS ) on G protein-regulated ion channels. RGS3 and RGS4 induced a substan tial increase in currents through the G beta gamma-regulated inwardly rectifying K+ channels, I-K(ACh), in the absence of receptor activatio n. Concomitantly, the amount of current that could be activated by ago nist was reduced. Pretreatment with pertussis toxin or a muscarinic re ceptor antagonist abolished agonist-induced currents but did not modif y RGS effects. Cotransfection of cells with a G beta gamma-binding pro tein significantly reduced the RGS4-induced basal I-K(ACh) currents. T he RGS proteins also modified the properties of another G beta gamma e ffector, the N-type Ca2+ channels. These observations strongly suggest that RGS proteins increase the availability of G beta gamma in additi on to their previously described GTPase-activating function.