Regulators of G protein signaling (RGS) proteins constitutively activate Gbeta 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 substantial increase in currents through the Gbeta gamma-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 Gbetagamma-binding protein significantly reduced the RGS4-induced basal IK(ACh) currents. The RGS proteins also modified the properties of another Gbeta gamma effector, the N-type Ca2+ channels. These observations strongly suggest that RGS proteins increase the availability of Gbeta gamma in addition to their previously described GTPase-activating function.
Bünemann
M
M
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Hosey
M M
MM
D015220:Calcium Channels / Q000378:metabolism; D004553:Electric Conductivity; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D018727:Muscarinic Antagonists / Q000494:pharmacology; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011506:Proteins / Q000378:metabolism*; D020710:RGS Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D020690:GTPase-Activating Proteins; D018727:Muscarinic Antagonists; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011506:Proteins; D020710:RGS Proteins; D011994:Recombinant Proteins; C415085:Rgs3 protein, mouse; D010566:Virulence Factors, Bordetella; C098799:RGS4 protein; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins