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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
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
Horowitz
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.
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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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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