Expression and motor functional roles of voltage-dependent type 7 K+ channels in the human taenia coli

Voltage dependent type 7 K+ (K(V)7 or KCNQ) channels modulate the excitability of neurons and muscle cells. The aims of the present study were to investigate the motor effects of K(V)7 channel modulators and the expression of K(V)7 channels in the human taenia coil. The effects of K(V)7 channel modulators on the muscle Lone of human taenia coli strips were investigated under nonadrenergic non-nitrergic conditions by organ bath studies. Gene expression and tissue localisation of channels were studied by real time PCR and immunohistochemistry, respectively. Under basal conditions, the K(V)7 channel blocker XE-991 induced concentration dependent contractions, with mean EC50 and E-max of 18.7 mu M and 30.5% respectively of the maximal bethanechol-induced contraction, respectively. The K(V)7 channel activators retigabine and flupirtine concentration dependently relaxed the taenia coli, with mean EC(50)s of 19.2 mu M and 29.9 mu M respectively. Retigabine also relaxed bethanechol-precontracted strips, with maximal relaxations of 79.2% of the bethanecol-induced precontraction. The motor effects induced by the K(V)7 channel modulators were not affected by tetrodotoxin or omega-conotoxin GVIA. XE-991 greatly reduced retigabine- and flupirtine-induced relaxations. Transcripts encoded by all KCNQ genes were detected in the taenia coli, with KCNQ4 showing the highest expression levels. K(V)7.4 channels were clearly visualised by immunohistochemistry in colonic epithelium, circular muscle layer and taenia coli. K(V)7 channels appear to contribute to the resting muscle tone of the human taenia coli. In addition, K(V)7 channel activators significantly relax the taenia colt. Thus, they could be useful therapeutic relaxant agents for colonic motor disorders. (C) 2013 Elsevier B.V. All rights reserved