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

详细信息    查看全文

• 作者：Alice Adduci ; Maria Martire ; Maurizio Taglialatela ; Vincenzo Arena ; Gianluca Rizzo ; Claudio Coco ; Diego Curr貌
• 关键词：KV7 channels ; KCNQ channels ; Retigabine ; taenia coli
• 刊名：European Journal of Pharmacology
• 出版年：5 December, 2013
• 年：2013
• 卷：721
• 期：1-3
• 页码：12-20
• 全文大小：5046 K

文摘

Voltage-dependent type 7 K⁺ (K_V7 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_V7 channel modulators and the expression of K_V7 channels in the human taenia coli. The effects of K_V7 channel modulators on the muscle tone 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_V7 channel blocker XE-991 induced concentration-dependent contractions, with mean EC₅₀ and E_max of 18.7 渭M and 30.5% respectively of the maximal bethanechol-induced contraction, respectively. The K_V7 channel activators retigabine and flupirtine concentration-dependently relaxed the taenia coli, with mean EC₅₀s of 19.2 渭M and 29.9 渭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_V7 channel modulators were not affected by tetrodotoxin or 蠅-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_V7.4 channels were clearly visualised by immunohistochemistry in colonic epithelium, circular muscle layer and taenia coli. K_V7 channels appear to contribute to the resting muscle tone of the human taenia coli. In addition, K_V7 channel activators significantly relax the taenia coli. Thus, they could be useful therapeutic relaxant agents for colonic motor disorders.