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 EC50 and Emax of 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.
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Acknowledgments
This study was supported by “Fondi di Ateneo” of the Catholic University of the Sacred Heart, Rome. The technical help of Ms. S. Catino (Institute of Pharmacology, Catholic University of the Sacred Heart, Rome, Italy) with the Western blot experiments is deeply acknowledged. The authors are indebted to Prof. M. Taglialatela (Department of Health Sciences, University of Molise, Campobasso, Italy), for the generous gift of retigabine and the antibody anti-KV7.5 channels, and to Mr. R. Donato for revision of English.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Bientinesi, R., Mancuso, C., Martire, M. et al. KV7 channels in the human detrusor: channel modulator effects and gene and protein expression. Naunyn-Schmiedeberg's Arch Pharmacol 390, 127–137 (2017). https://doi.org/10.1007/s00210-016-1312-9
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DOI: https://doi.org/10.1007/s00210-016-1312-9