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Heterologously expressed serotonin 1A receptors couple to muscarinic K+ channels in heart

Karschin, Andreas and Ho, Begonia Y. and Labarca, Cesar and Elroy-Stein, Orna and Moss, Bernard and Davidson, Norman and Lester, Henry A. (1991) Heterologously expressed serotonin 1A receptors couple to muscarinic K+ channels in heart. Proceedings of the National Academy of Sciences of the United States of America, 88 (13). pp. 5694-5698. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:KARpnas91

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Abstract

In cardiac atrial cells, muscarinic acetylcholine receptors activate a K+ current directly via a guanine nucleotide-binding protein (G protein). Serotonin type 1A receptors may activate a similar pathway in hippocampal neurons. To develop a system in which receptor/G protein/K+ channel coupling can be experimentally manipulated, we have used a highly efficient recombinant vaccinia virus vector system to express human serotonin 1A receptors in primary cultures of rat atrial myocytes. The expressed 1A receptors activated the inwardly rectifying K+ conductance that is normally activated by the endogenous muscarinic acetylcholine receptors. Maximal responses to either agonist occluded further activation by the other agonist. The average activation time constants for serotonin were about 5 times slower than for acetylcholine. The data support suggestions that the intracellular signaling pathway from seven-helix receptors to G proteins and directly to ion channels is widespread in excitable cells. After a fraction of the G proteins are activated irreversibly by guanosine 5'-[γ-thio]triphosphate, subsequent transduction proceeds more efficiently. One possible interpretation is that multiple G-protein molecules are required to activate each channel. Vaccinia virus expression vectors are thus useful for expressing seven-helix receptors in primary cultures of postmitotic cells and have provided a heterologous expression system for the signaling pathway from seven-helix receptors to G proteins and directly to ion channels.


Item Type:Article
Additional Information:© 1991 by the National Academy of Sciences. Contributed by Norman Davidson, April 2, 1991. We thank R. Weinshank and P. Hartig for the human 5-HT1AR cDNA; T. Branchek and N. Adham for performing some binding experiments; and A. Gouin, E. Kwon, C. Nolan, and M. King for expert assistance. This work was supported by the National Institutes of Health (GM29836 and GM10991) and the Cystic Fibrosis Foundation and by fellowships from the Max Kade Foundation and Alexander von Humboldt Stiftung (A.K.) and the American Heart Association (B.Y.H.). 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:VACCINIA VIRUS EXPRESSION; GUANINE NUCLEOTIDE-BINDING PROTEINS; 7-HELIX RECEPTORS; ATRIAL CELLS; ACETYLCHOLINE
Record Number:CaltechAUTHORS:KARpnas91
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:KARpnas91
Alternative URL:http://dx.doi.org/10.1073/pnas.88.13.5694
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7540
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:02 Mar 2007
Last Modified:14 Nov 2014 19:19

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