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Atrial G protein-activated K+ channel: expression cloning and molecular properties

Dascal, Nathan and Schreibmayer, Wolfgang and Lim, Nancy F. and Wang, Weizhen and Chavkin, Charles and DiMagno, Lisa and Labarca, Cesar and Kieffer, Brigitte L. and Gaveriaux-Ruff, Claire and Trollinger, David and Lester, Henry A. and Davidson, Norman (1993) Atrial G protein-activated K+ channel: expression cloning and molecular properties. Proceedings of the National Academy of Sciences of the United States of America, 90 (21). pp. 10235-10239. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:DASpnas93b

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Abstract

Activity of several ion channels is controlled by heterotrimeric GTP-binding proteins (G proteins) via a membrane-delimited pathway that does not involve cytoplasmic intermediates. The best studied example is the K+ channel activated by muscarinic agonists in the atrium, which plays a crucial role in regulating the heartbeat. To enable studies of the molecular mechanisms of activation, this channel, denoted KGA, was cloned from a rat atrium cDNA library by functional coupling to coexpressed serotonin type 1A receptors in Xenopus oocytes. KGA displays regions of sequence homology to other inwardly rectifying channels as well as unique regions that may govern G-protein interaction. The expressed KGA channel is activated by serotonin 1A, muscarinic m2, and delta-opioid receptors via G proteins. KGA is activated by guanosine 5'-[gamma-thio]triphosphate in excised patches, confirming activation by a membrane-delimited pathway, and displays a conductance equal to that of the endogenous channel in atrial cells. The hypothesis that similar channels play a role in neuronal inhibition is supported by the cloning of a nearly identical channel (KGB1) from a rat brain cDNA library.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.90.21.10235DOIUNSPECIFIED
http://www.pnas.org/content/90/21/10235PublisherUNSPECIFIED
Additional Information:© 1993 by the National Academy of Sciences. Contributed by Norman Davidson, July 28, 1993. We thank Jun Li for preparing some of the cDNAs and P. Hartig, M. I. Simon, and E. Peralta for supplying the cDNAs of 5HT1A receptor, Gi2 α subunit, and m2 receptor, respectively. This work was supported by Public Health Service Grants GM29836, MH49176, and DA04123 (C.C.), by the U.S.-Israel Binational Science Foundation, and by the Austrian Research Foundation. The sequences reported in this paper have been deposited in the GenBank database (accession nos. U01071 for KGA and U01141 for KGB1). 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.
Funders:
Funding AgencyGrant Number
Public Health ServiceGM29836
Public Health ServiceMH49176
Public Health ServiceDA04123
U.S.-Israel Binational Science FoundationUNSPECIFIED
Austrian Research FoundationUNSPECIFIED
Subject Keywords:GTP-BINDING PROTEINS; DELTA-OPIOID RECEPTOR; ION CHANNELS; MUSCARINIC RECEPTORS; GAMMA-SUBUNIT; CELLS; SEROTONIN; HEART; HIPPOCAMPUS; MEMBRANE
Record Number:CaltechAUTHORS:DASpnas93b
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:DASpnas93b
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:12194
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:13 Nov 2008 03:26
Last Modified:26 Dec 2012 10:28

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