Functional and Molecular Evidence for K(v)7 Channel Subtypes in Human Detrusor from Patients with and without Bladder Outflow Obstruction

The aim of the study was to investigate whether K(v)7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. K(v)7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expression of KCNQ1, KCNQ3-KCNQ5 and KCNE1-5 in the human urinary bladder from patients with normal bladder function (n = 7) and in patients with bladder outflow obstruction (n = 3). Interestingly, a 3.4-fold up-regulation of KCNQ1 was observed in the latter. The K(v)7 channel subtype selective modulators, ML277 (activator of K(v)7.1 channels, 10 μM) and ML213 (activator of K(v)7.2, K(v)7.4, K(v)7.4/7.5 and K(v)7.5 channels, 10 μM), reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of K(v)7.1–7.5 channels, 10 μM) had opposing effects as it increased contractions achieved with 20 mM KPSS. Furthermore, we investigated if there is interplay between K(v)7 channels and β-adrenoceptors. Using cumulative additions of isoprenaline (β-adrenoceptor agonist) and forskolin (adenylyl cyclase activator) in combination with the K(v)7 channel activator and blocker, retigabine and XE991, we did not find interplay between K(v)7 channels and β-adrenoceptors in the human urinary bladder. The performed gene expression analysis combined with the organ bath studies imply that compounds that activate K(v)7 channels could be useful for treatment of overactive bladder syndrome.