Abstract
Aims We investigated the roles of neuronal-derived nitric oxide (NO) in the modulation of spontaneous activity of mouse detrusor smooth muscle. Methods Detrusor smooth muscle strips were isolated from nNOS gene knock-out (nNOS ) mice and their wild type siblings (nNOS ). The properties of smooth muscle cells were assessed using intracellular electrophysiology and Ca imaging by laser-scanning confocal microscopy. The effects of an nNOS inhibitor, 7-nitro indazole (7-NI) on electrically evoked contractility were assessed using nNOS mouse detrusor strips. Results In spontaneously active cells, the frequency of spontaneous action potentials (sAPs) and whole cell Ca flashes in nNOS preparations was lower than that in the nNOS preparations. The frequency of sAPs was enhanced by a nitric oxide donor, diethylamine NONOate sodium salt (NONOate; 100μM), both when used alone and when the cGMP pathway was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, 10μM). 7-NI (100μM) significantly suppressed the electrically evoked contraction of mouse detrusor strips. Conclusions We suggest that neuronal-derived NO facilitates the generation of spontaneous activity via a cGMP-independent pathway, and consequently enhances the evoked contraction of detrusor. Dysregulation of nNOS containing nerves may underlie bladder pathologies. Copyright © 2012 Wiley Periodicals, Inc.