Regulators of G Protein Signaling (RGS) Proteins Constitutively Activate Gβγ-gated Potassium Channels

doi:10.1074/jbc.273.47.31186

Regulators of G Protein Signaling (RGS) Proteins Constitutively Activate Gβγ-gated Potassium Channels*

From the Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611

Abstract

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,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 Gβγ-binding protein significantly reduced the RGS4-induced basalI _K(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.

Footnotes

↵* This work was supported by National Institutes of Health Grant HL50121 (to M. M. H.) and Research Fellowship BU 1133/1-1 (to M. B.) from the Deutsche Forschungsgemeinschaft.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵‡ To whom correspondence should be addressed: Dept. of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Ave. S-215, Chicago, IL 60611. Tel.: 312-503-3692; Fax: 312-503-5349; E-mail: mhosey{at}nwu.edu.
Abbreviations:

RGS

regulators of G protein signaling

GAP

GTPase-activating protein

GIRK

G protein-regulated inwardly rectifying K⁺ channels

mAChRs

muscarinic acetylcholine receptors

HEK

human embryonic kidney

CHO

Chinese hamster ovary

ACh

acetylcholine

F

farad.
- Received September 3, 1998.
The American Society for Biochemistry and Molecular Biology, Inc.