Role of neuronal voltage-gated K(+) channels in the modulation of the nitrergic neurotransmission of the pig urinary bladder neck.
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.
Hernández
M
M
Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain. medardo@farm.ucm.es
Barahona
M V
MV
Recio
P
P
Navarro-Dorado
J
J
Bustamante
S
S
Benedito
S
S
García-Sacristán
A
A
Prieto
D
D
Orensanz
L M
LM
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*
D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D012977:Sodium Nitrite