title: The actions of metabolic inhibition on human detrusor smooth muscle contractility from stable and unstable bladders.
abstract: OBJECTIVE
  To determine the important cellular site(s) of action of a brief exposure to NaCN (chosen to reduce mitochondrial respiration and hence mimic cellular hypoxia) on the mechanical properties and regulation of intracellular [Ca2+] in human detrusor smooth muscle. Using muscle samples obtained from patients with stable and unstable bladders, to determine whether the unstable bladder is associated with changes in the functional properties of detrusor muscle under these circumstances. Materials and methods Experiments were conducted in vitro on muscle strips or isolated cells. Isometric tension was recorded in muscle strips during electrical stimulation or exposure to agonists. Intracellular [Ca2+] and [H+] were measured by epifluorescence microscopy, and cell autofluorescence measured as an index of mitochondrial function.
  
  
  RESULTS
  There were no differences in the responses to electrical stimulation and varying concentrations of carbachol in muscle strips from stable and unstable bladders. NaCN (2 mmol/L) reduced the contraction induced by carbachol (10 micromol/L) by a mean (SD) of 43 (16)% and 56 (15)% in the two groups; the reduction in the unstable was significantly less than in the stable group. NaCN similarly reduced the response to 10 mmol/L caffeine, but had no effect on the KCl-induced contraction. NaCN significantly increased the resting sarcoplasmic [Ca2+] and attenuated the calcium transients evoked by carbachol and caffeine, but again had no effect on the KCl-induced transient. The reduction of the carbachol calcium transient was also less in cells from unstable bladders than in those from stable bladders. There was no effect of NaCN on intracellular pH, except for a brief, transient alkalosis.
  
  
  CONCLUSIONS
  NaCN reduces both the contraction and Ca-transient to carbachol by reducing Ca2+ accumulation by intracellular stores, because the carbachol- and caffeine-evoked responses were similar. Any effect on transmembrane Ca2+ flux was minimal because there was no effect on KCl-induced responses. The greater resilience of tissue from unstable bladders to acute cellular hypoxia may reflect some adaptation acquired in vivo.
authors.affiliation: The Institute of Urology & Nephrology, London, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Hockey
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.forename: C H
authors.initials: CH
authors.lastname: Fry
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D012966:Sodium Cyanide / Q000494:pharmacology; D001745:Urinary Bladder Diseases / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D002217:Carbachol; D012966:Sodium Cyanide; D002118:Calcium