title: Functional and molecular evidence for Kv7 channel subtypes in human detrusor from patients with and without bladder outflow obstruction.
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.
authors.affiliation: Smooth Muscle Research Center, Department of Clinical Biochemistry, Copenhagen University Hospital, Koege, Denmark; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Julie
authors.initials: J
authors.lastname: Svalø
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Majid
authors.initials: M
authors.lastname: Sheykhzade
authors.affiliation: Department of Urology, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Nordling
authors.affiliation: Department of Urology, Copenhagen University Hospital, Naestved, Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Matras
authors.affiliation: Smooth Muscle Research Center, Department of Clinical Biochemistry, Copenhagen University Hospital, Koege, Denmark.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bouchelouche
mesh_terms: D000368:Aged; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D051656:KCNQ Potassium Channels / 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 / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D051656:KCNQ Potassium Channels; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D007545:Isoproterenol