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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/G107    most recent 00057.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Jepps, T. A. Articles by Ohya, S. PubMed PubMed Citation Articles by Jepps, T. A. Articles by Ohya, S.

NEUROREGULATION AND MOTILITY

Molecular and functional characterization of K_v7 K⁺ channel in murine gastrointestinal smooth muscles

¹Division of Basic Medical Sciences, St George's, University of London, London, United Kingdom; ²Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada; and ³Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Submitted 12 February 2009 ; accepted in final form 16 April 2009

Members of the K_v7 voltage-gated K⁺ channel family are important determinants of cardiac and neuronal membrane excitability. Recently, we and others have shown that K_v7 channels are also crucial regulators of smooth muscle activity. The aim of the present study was to assess the K_v7 expression in different parts of the murine gastrointestinal (GI) tract and to assess their functional roles by use of pharmacological agents. Of KCNQ/K_v7 members, both KCNQ4/K_v7.4 and KCNQ5/K_v7.5 genes and proteins were the most abundantly expressed K_v7 channels in smooth muscles throughout the GI tract. Immunohistochemical staining also revealed that K_v7.4 and K_v7.5 but not K_v7.1 were expressed in the circular muscle layer of the colon. In segments of distal colon circular muscle exhibiting spontaneous phasic contractions, the nonselective K_v7 blockers XE991 and linopirdine increased the integral of tension. Increases in the integral of tension were also observed under conditions of neuronal blockade. Similar effects, although less marked, were observed in the proximal colon. As expected, the K_v7.1-selective blocker chromanol 293B had no effect in either type of segment. These data show that K_v7.x especially K_v7.4 and K_v7.5 are expressed in different regions of the murine gastrointestinal tract and blockers of K_v7 channels augment inherent contractile activity. Drugs that selectively block K_v7.4/7.5 might be promising therapeutics for the treatment of motility disorders such as constipation associated with irritable bowel syndrome.

colon; voltage-gated K⁺ channel; KCNE