Functional and Molecular Evidence for Kv7 Channel Subtypes in Human Detrusor from Patients with and without Bladder Outflow Obstruction

The aim of the study was to investigate whether K_v7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. K_v7 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_v7 channel subtype selective modulators, ML277 (activator of K_v7.1 channels, 10 μM) and ML213 (activator of K_v7.2, K_v7.4, K_v7.4/7.5 and K_v7.5 channels, 10 μM), reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of K_v7.1–7.5 channels, 10 μM) had opposing effects as it increased contractions achieved with 20 mM KPSS. Furthermore, we investigated if there is interplay between K_v7 channels and β-adrenoceptors. Using cumulative additions of isoprenaline (β-adrenoceptor agonist) and forskolin (adenylyl cyclase activator) in combination with the K_v7 channel activator and blocker, retigabine and XE991, we did not find interplay between K_v7 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_v7 channels could be useful for treatment of overactive bladder syndrome.