title: KV7 channels in the human detrusor: channel modulator effects and gene and protein expression.
abstract: Voltage-gated type 7 K+(KV7 or KCNQ) channels regulate the contractility of various smooth muscles. With this study, we aimed to assess the role of KV7 channels in the regulation of human detrusor contractility, as well as the gene and protein expression of KV7 channels in this tissue. For these purposes, the isolated organ technique, RT-qPCR, and Western blot were used, respectively. XE-991, a selective KV7 channel blocker, concentration-dependently contracted the human detrusor; mean EC50and Emaxof XE-991-induced concentration-response curve were 14.1 μM and 28.8 % of the maximal bethanechol-induced contraction, respectively. Flupirtine and retigabine, selective KV7.2-7.5 channel activators, induced concentration-dependent relaxations of bethanechol-precontracted strips, with maximal relaxations of 51.6 and 51.8 % of the precontraction, respectively. XE-991 blocked the relaxations induced by flupirtine and retigabine. All five KCNQ genes were found to be expressed in the detrusor with KCNQ4 being the most expressed among them. Different bands, having sizes similar to some of reported KV7.1, 7.4, and 7.5 channel subunit isoforms, were detected in the detrusor by Western blot with the KV7.4 band being the most intense among them. In conclusion, KV7 channels contribute to set the basal tone of the human detrusor. In addition, KV7 channel activators significantly relax the detrusor. The KV7.4 channels are probably the most important KV7 channels expressed in the human detrusor. These data suggest that selective KV7.4 channel activators might represent new pharmacological tools for inducing therapeutic relaxation of the detrusor.
authors.affiliation: Department of Surgical Sciences, School of Medicine, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bientinesi
authors.affiliation: Institute of Pharmacology, School of Medicine, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Mancuso
authors.affiliation: Institute of Pharmacology, School of Medicine, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Martire
authors.affiliation: Department of Surgical Sciences, School of Medicine, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: Pier Francesco
authors.initials: PF
authors.lastname: Bassi
authors.affiliation: Department of Surgical Sciences, School of Medicine, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Sacco
authors.affiliation: Institute of Pharmacology, School of Medicine, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy. diego.curro@unicatt.it.
authors.forename: Diego
authors.identifier: http://orcid.org/0000-0001-6726-6872
authors.initials: D
authors.lastname: Currò
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D051656:KCNQ Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051658:KCNQ2 Potassium Channel / Q000235:genetics / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*
chemical_list: D051656:KCNQ Potassium Channels; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; C117367:KCNQ4 protein, human; C412231:KCNQ5 protein, human; D026902:Potassium Channel Blockers
keywords: Flupirtine; Human detrusor; KCNQ channels; KV7 channels; Retigabine; XE-991