title: Role of neuronal voltage-gated K(+) channels in the modulation of the nitrergic neurotransmission of the pig urinary bladder neck.
abstract: OBJECTIVE
  As nitric oxide (NO) plays an essential role in the inhibitory neurotransmission of the bladder neck of several species, the current study investigates the mechanisms underlying the NO-induced relaxations in the pig urinary bladder neck.
  
  
  METHODS
  Urothelium-denuded bladder neck strips were dissected and mounted in isolated organ baths containing a physiological saline solution at 37 degrees C and continuously gassed with 5% CO(2) and 95% O(2), for isometric force recording. The relaxations to transmural nerve stimulation (EFS), or to exogenously applied acidified NaNO(2) solution were carried out on strips pre-contracted with phenylephrine, and treated with guanethidine and atropine, to block noradrenergic neurotransmission and muscarinic receptors, respectively.
  
  
  RESULTS
  EFS (0.2-1 Hz) and addition of acidified NaNO(2) solution (1 microM-1 mM) evoked frequency- and concentration-dependent relaxations, respectively. These responses were potently reduced by the blockade of guanylate cyclase and were not modified by the K(+) channel blockers iberiotoxin, charybdotoxin, apamin or glibenclamide. The voltage-gated K(+) (Kv) channels inhibitor 4-aminopyridine, greatly enhanced the nitrergic relaxations evoked by EFS, but did not affect the NaNO(2) solution-induced relaxations.
  
  
  CONCLUSIONS
  NO, whose release is modulated by pre-junctional Kv channels, relaxes the pig urinary bladder neck through a mechanism dependent on the activation of guanylate cyclase, in which post-junctional K(+) channels do not seem to be involved. Modulation of Kv channels could be useful in the therapy of the urinary incontinence produced by intrinsic sphincteric deficiency.
authors.affiliation: Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain. medardo@farm.ucm.es
authors.forename: M
authors.initials: M
authors.lastname: Hernández
authors.forename: M V
authors.initials: MV
authors.lastname: Barahona
authors.forename: P
authors.initials: P
authors.lastname: Recio
authors.forename: J
authors.initials: J
authors.lastname: Navarro-Dorado
authors.forename: S
authors.initials: S
authors.lastname: Bustamante
authors.forename: S
authors.initials: S
authors.lastname: Benedito
authors.forename: A
authors.initials: A
authors.lastname: García-Sacristán
authors.forename: D
authors.initials: D
authors.lastname: Prieto
authors.forename: L M
authors.initials: LM
authors.lastname: Orensanz
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine; D001743:Urinary Bladder / Q000294:innervation / Q000378:metabolism*
chemical_list: D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D012977:Sodium Nitrite