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 Gβγ-regulated inwardly rectifying K+ channels,IK(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 Gβγ-binding protein significantly reduced the RGS4-induced basalIK(ACh) currents. The RGS proteins also modified the properties of another Gβγ effector, the N-type Ca2+ channels. These observations strongly suggest that RGS proteins increase the availability of Gβγ in addition to their previously described GTPase-activating function.