Abstract
The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 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 Kv7 channel subtype selective modulators, ML277 (activator of Kv7.1 channels, 10 μM) and ML213 (activator of Kv7.2, Kv7.4, Kv7.4/7.5 and Kv7.5 channels, 10 μM), reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of Kv7.1–7.5 channels, 10 μM) had opposing effects as it increased contractions achieved with 20 mM KPSS. Furthermore, we investigated if there is interplay between Kv7 channels and β-adrenoceptors. Using cumulative additions of isoprenaline (β-adrenoceptor agonist) and forskolin (adenylyl cyclase activator) in combination with the Kv7 channel activator and blocker, retigabine and XE991, we did not find interplay between Kv7 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 Kv7 channels could be useful for treatment of overactive bladder syndrome.
Highlights
The physiological roles of the urinary bladder are storage of urine and micturition
All KCNQ and KCNE subtypes were detected in human urinary bladder biopsies, except for KCNQ2 in which only one patient had a level of KCNQ2 that was above the detection limit (Cq
Are Kv7 channels functionally present in the human urinary bladder, they are active at low level of depolarisation since XE991 augmented the pre-constriction tone achieved with 20 mM KPSS, but had no effect on the pre-constriction tone achieved with 40 mM KPSS- or 1 μM carbachol
Summary
The physiological roles of the urinary bladder are storage of urine and micturition. These processes are controlled both locally, by receptors in smooth muscle cells, urothelium and nerves, and centrally by higher brain levels [1]. Kv7 Channels in the Human Urinary Bladder a number of diseases are linked to the lower urinary tract system. One of these diseases is overactive bladder (OAB) syndrome. It is a symptom complex that is defined by urgency, with or without urinary incontinence, nocturia and daytime urinary frequency, all symptoms that are related to the storage of urine [2]. A recent approval of the β3-adrenoceptor agonist mirabegron by the FDA has improved the prospects for OAB patients [5]
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