K⁺ channels as potential targets for the treatment of gastrointestinal motor disorders

详细信息    查看全文

• 作者：Diego Currò ; ; ^{dcurro@rm.unicatt.it" class="auth_mail}
• 关键词：4-Aminopyridine (PubChem CID ; 1727) ; Apamin (PubChem CID ; 16218850) ; DMP-543 (PubChem CID ; 9887884) ; E-4031 (PubChem CID ; 3185) ; Flupirtine (PubChem CID ; 53276) ; Iberiotoxin (PubChem CID ; 16132435) ; Linopirdine (PubChem CID ; 3932) ; Retigabine (PubChem CID ; 121892) ; Tetraethylammonium (PubChem CID ; 5413) ; XE-991 (PubChem CID ; 656732)
• 刊名：European Journal of Pharmacology
• 出版年：15 June 2014
• 年：2014
• 卷：733
• 期：Complete
• 页码：97-101
• 全文大小：437 K

文摘

K⁺ channels play important functional roles in excitable cells, as neurons and muscle cells. The activation or inhibition of K⁺ channels hyperpolarizes or depolarizes the cell membrane, respectively. These effects determine in the smooth muscle decrease or increase in Ca²⁺ influx through voltage-gated Ca²⁺ (Ca_V1.2) channels and relaxation or contraction, respectively. Recent studies highlight the importance of voltage-dependent type 7 K⁺ (K_V7 or KCNQ) channels in regulating muscle tone and contractility in stomach and colon. K_V7 channels, that include 5 subtypes (K_V7.1–7.5), are activated at relatively negative potential values, close to those of the resting membrane potential for the smooth muscle cells of some segments of the gastrointestinal tract. Thus, they contribute to set the resting membrane potential and their blockade induces increase in smooth muscle contractility in stomach and colon. In addition, K_V7 channel activation produces profound relaxations of gastric and colonic smooth muscle. Therefore, K_V7 channel activators could be used to relax the smooth muscle and relieve symptoms in diseases such as functional dyspepsia and irritable bowel syndrome with prevalent diarrhea. The discovery of activators selective for the channel subtypes present in the smooth muscle, mainly K_V7.4 and 7.5, would allow avoiding adverse cardiac and nervous system effects. A further step forward would be characterizing putative differences among the K_V7 channel subtypes expressed in the various smooth muscles and synthesizing molecules specific for the gastrointestinal smooth muscle.