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Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by Gβγ subunits and function as heteromultimers

Kofuji, Paulo and Davidson, Norman and Lester, Henry A. (1995) Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by Gβγ subunits and function as heteromultimers. Proceedings of the National Academy of Sciences of the United States of America, 92 (14). pp. 6542-6546. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:KOFpnas95

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Abstract

Guanine nucleotide-binding proteins (G proteins) activate K+ conductances in cardiac atrial cells to slow heart rate and in neurons to decrease excitability. cDNAs encoding three isoforms of a G-protein-coupled, inwardly rectifying K+ channel (GIRK) have recently been cloned from cardiac (GIRK1/Kir 3.1) and brain cDNA libraries (GIRK2/Kir 3.2 and GIRK3/Kir 3.3). Here we report that GIRK2 but not GIRK3 can be activated by G protein subunits Gβ1 and G2 in Xenopus oocytes. Furthermore, when either GIRK3 or GIRK2 was coexpressed with GIRK1 and activated either by muscarinic receptors or by Gβ subunits, G-protein-mediated inward currents were increased by 5- to 40-fold. The single-channel conductance for GIRK1 plus GIRK2 coexpression was intermediate between those for GIRK1 alone and for GIRK2 alone, and voltage-jump kinetics for the coexpressed channels displayed new kinetic properties. On the other hand, coexpression of GIRK3 with GIRK2 suppressed the GIRK2 alone response. These studies suggest that formation of heteromultimers involving the several GIRKs is an important mechanism for generating diversity in expression level and function of neurotransmitter-coupled, inward rectifier K+ channels.


Item Type:Article
Additional Information:© 1995 by the National Academy of Sciences. Contributed by Norman Davidson, April 10, 1995. We thank Brad Henkle for preparing the oocytes, Craig Doupnik and Yinong Zhang for advice, and Dr. Michel Lazdunski for sharing a preprint of ref. 22 while it was in press. This work was supported by ICAgen, Inc., and by National Institutes of Health Grants GM29836 and MH49176. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:DORSAL RAPHE NEURONS; POTASSIUM CHANNELS; RECEPTORS; EXPRESSION; BINDING; HEART; HIPPOCAMPUS; SEROTONIN; CURRENTS; INVITRO
Record Number:CaltechAUTHORS:KOFpnas95
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:KOFpnas95
Alternative URL:http://dx.doi.org/10.1073/pnas.92.14.6542
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9187
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:20 Nov 2007
Last Modified:26 Dec 2012 09:46

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