TREK-1 Regulation by Nitric Oxide and cGMP-dependent Protein Kinase

• Published in: The Journal of biological chemistry Vol. 276; no. 47; pp. 44338 - 44346
• Main Authors: Koh, Sang Don, Monaghan, Kevin, Sergeant, Gerard P., Ro, Seungil, Walker, Rebecca L., Sanders, Kenton M., Horowitz, Burton
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 23-11-2001; American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M108125200

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 10−5m) and 8-Br-cGMP (10−4 or 10−3m) 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.