title: Effects of potassium channel modulators on myogenic spontaneous phasic contractile activity in human detrusor from neurogenic patients.
abstract: OBJECTIVE
  To characterize the spontaneous contractile activity (SCA) developed by detrusor from patients with neurogenic detrusor overactivity (NDO) because the alteration of detrusor properties plays a critical role in the pathogenesis of detrusor overactivity, as well as to evaluate the role of K(ATP) and K(Ca) channels on this SCA because these channels regulate detrusor SCA in many species, including humans without overactive bladder (OAB).
  
  
  METHODS
  Human bladder samples were obtained from 44 patients undergoing cystectomy for bladder cancer with no known OAB symptoms and from 38 patients suffering from urodynamically diagnosed NDO. Detrusor strips with or without urothelium/suburothelium were mounted isometrically in organ baths filled with Krebs-HEPES (37 °C; 95% O(2) /5% CO(2) ). Strips were incubated with 10 µm pinacidil (K(ATP) opener) followed by 10 µm glibenclamide (K(ATP) blocker). In another set of experiments, strips were incubated with 30 µm NS-1619 (BK(Ca) opener) followed by 100 nm iberiotoxin (BK(Ca) blocker) or with 100 nm apamin (SK(Ca) blocker).
  
  
  RESULTS
  SCA occurred more frequently with larger amplitude and area under the curve in detrusor strips from NDO patients compared to control patients. The presence of urothelium/suburothelium did not significantly modify SCA in either patient population. Pinacidil markedly inhibited SCA of detrusor strips from control and NDO patients. This effect was reversed by glibenclamide. By contrast, NS-1619 followed by iberiotoxin did not elicit any significant changes in SCA from NDO patients, contrary to control patients.
  
  
  CONCLUSIONS
  K(ATP) and SK(Ca) channels regulate SCA of NDO patients' detrusor strips. By contrast, BK(Ca) channels are not involved in the regulation of detrusor SCA in NDO patients, whereas they regulate SCA in control patients. These results should be considered in the development of K(+) channels openers for the treatment of NDO. Moreover, SCA observed in vitro should be regarded as an in vitro modelling of human NDO.
authors.affiliation: Pelvipharm, Orsay Parc Bat Cèdre, Orsay, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Oger
authors.forename: Delphine
authors.initials: D
authors.lastname: Behr-Roussel
authors.forename: Diane
authors.initials: D
authors.lastname: Gorny
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernabé
authors.forename: Eva
authors.initials: E
authors.lastname: Comperat
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chartier-Kastler
authors.forename: Pierre
authors.initials: P
authors.lastname: Denys
authors.forename: Francois
authors.initials: F
authors.lastname: Giuliano
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000368:Aged; D001030:Apamin / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D016022:Case-Control Studies; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D019459:Urothelium / Q000187:drug effects
chemical_list: D001562:Benzimidazoles; D049990:Membrane Transport Modulators; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C086491:NS 1619; D001030:Apamin; C064719:iberiotoxin; D020110:Pinacidil; D005905:Glyburide