title: Functional expression of KCNQ (Kv7) channels in guinea pig bladder smooth muscle and their contribution to spontaneous activity.
abstract: OBJECTIVE
  The aim of the study was to determine whether KCNQ channels are functionally expressed in bladder smooth muscle cells (SMC) and to investigate their physiological significance in bladder contractility.
  
  
  METHODS
  KCNQ channels were examined at the genetic, protein, cellular and tissue level in guinea pig bladder smooth muscle using RT-PCR, immunofluorescence, patch-clamp electrophysiology, calcium imaging, detrusor strip myography, and a panel of KCNQ activators and inhibitors.
  
  
  RESULTS
  KCNQ subtypes 1-5 are expressed in bladder detrusor smooth muscle. Detrusor strips typically displayed TTX-insensitive myogenic spontaneous contractions that were increased in amplitude by the KCNQ channel inhibitors XE991, linopirdine or chromanol 293B. Contractility was inhibited by the KCNQ channel activators flupirtine or meclofenamic acid (MFA). The frequency of Ca²⁺-oscillations in SMC contained within bladder tissue sheets was increased by XE991. Outward currents in dispersed bladder SMC, recorded under conditions where BK and KATP currents were minimal, were significantly reduced by XE991, linopirdine, or chromanol, and enhanced by flupirtine or MFA. XE991 depolarized the cell membrane and could evoke transient depolarizations in quiescent cells. Flupirtine (20 μM) hyperpolarized the cell membrane with a simultaneous cessation of any spontaneous electrical activity.
  
  
  CONCLUSIONS
  These novel findings reveal the role of KCNQ currents in the regulation of the resting membrane potential of detrusor SMC and their important physiological function in the control of spontaneous contractility in the guinea pig bladder.
authors.affiliation: Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: U A
authors.initials: UA
authors.lastname: Anderson
authors.forename: C
authors.initials: C
authors.lastname: Carson
authors.forename: L
authors.initials: L
authors.lastname: Johnston
authors.forename: S
authors.initials: S
authors.lastname: Joshi
authors.forename: A M
authors.initials: AM
authors.lastname: Gurney
authors.forename: K D
authors.initials: KD
authors.lastname: McCloskey
mesh_terms: D000818:Animals; D017849:Animals, Inbred Strains; D020013:Calcium Signaling; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena / Q000187:drug effects; D015870:Gene Expression; D006168:Guinea Pigs; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051656:KCNQ Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D049990:Membrane Transport Modulators / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009213:Myography; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D059010:Single-Cell Analysis; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D051656:KCNQ Potassium Channels; D049990:Membrane Transport Modulators; D026902:Potassium Channel Blockers; D020033:Protein Isoforms