Regulators of G protein signaling (RGS) proteins constitutively activate Gβγ-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 substantial increase in currents through the G beta gamma-regulated inwardly rectifying K+ channels, I-K(ACh), in the absence of receptor activation. Concomitantly, the amount of current that could be activated by agonist was reduced. Pretreatment with pertussis toxin or a muscarinic receptor antagonist abolished agonist-induced currents but did not modify RGS effects. Cotransfection of cells with a G beta gamma-binding protein significantly reduced the RGS4-induced basal I-K(ACh) currents. The RGS proteins also modified the properties of another G beta gamma effector, the N-type Ca2+ channels. These observations strongly suggest that RGS proteins increase the availability of G beta gamma in addition to their previously described GTPase-activating function.