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Originally published In Press as doi:10.1074/jbc.M108125200 on September 17, 2001

J. Biol. Chem., Vol. 276, Issue 47, 44338-44346, November 23, 2001
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TREK-1 Regulation by Nitric Oxide and cGMP-dependent Protein Kinase
AN ESSENTIAL ROLE IN SMOOTH MUSCLE INHIBITORY NEUROTRANSMISSION*

Sang Don Koh, Kevin Monaghan, Gerard P. Sergeant, Seungil Ro, Rebecca L. Walker, Kenton M. Sanders, and Burton HorowitzDagger

From the Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557

Potassium channels activated by membrane stretch may contribute to maintenance of relaxation of smooth muscle cells in visceral hollow organs. Previous work has identified K+ channels in murine colon that are activated by stretch and further regulated by NO-dependent mechanisms. We have screened murine gastrointestinal, vascular, bladder, and uterine smooth muscles for the expression of TREK and TRAAK mRNA. Although TREK-1 was expressed in many of these smooth muscles, TREK-2 was expressed only in murine antrum and pulmonary artery. TRAAK was not expressed in any smooth muscle cells tested. Whole cell currents from TREK-1 expressed in mammalian COS cells were activated by stretch, and single channel recordings showed that the stretch-dependent conductance was due to 90 pS channels. Sodium nitroprusside (10-6 or 10-5 M) and 8-Br-cGMP (10-4 or 10-3 M) increased TREK-1 currents in perforated whole cell and single channel recordings. Mutation of the PKG consensus sequence at serine 351 blocked the stimulatory effects of sodium nitroprusside and 8-Br-cGMP on open probability without affecting the inhibitory effects of 8-Br-cAMP. TREK-1 encodes a component of the stretch-activated K+ conductance in smooth muscles and may contribute to nitrergic inhibition of gastrointestinal muscles.


* This work was supported by National Institutes of Health Grants DK 41315 and HL 49254.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.

Dagger To whom correspondence should be addressed. Tel.: 775-784-1462; Fax: 775-784-6903; E-mail: burt@physio.unr.edu.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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