Spontaneous contractions of the pig urinary bladder: the effect of ATP-sensitive potassium channels and the role of the mucosa

To investigate the influence of the mucosa on the inhibitory effects of the ATP-sensitive potassium channel (K(ATP) channel) opener, cromakalim, on the spontaneous contractions of pig bladder strips from the bladder dome and trigone. Little is known about the influence of the mucosa on spontaneous contractions and whether the nature of these contractions differs between the bladder dome and trigone. Paired longitudinal strips of female pig bladders were isolated from the dome and trigone. The mucosa was removed from one strip per pair and tissues were set up in organ baths. Spontaneous activity was allowed to develop and recorded, and then cumulative concentration-response curves to cromakalim were obtained. The time needed for spontaneous contractions to develop, the frequency and amplitude of spontaneous contractions, and the effect of cromakalim were analysed. The strips of mucosa removed from the dome to produce denuded strips were also analysed by immunofluorescence using antibodies specific for vimentin and alpha-smooth muscle actin (alpha-SMA). In the dome removal of the mucosa delayed the development of spontaneous contractions compared with mucosa-intact strips, whilst the trigone strips developed spontaneous contractions soon after set up in the organ baths irrespective of the presence or absence of mucosa. In the dome, cromakalim was more potent in suppressing spontaneous contractions when the mucosa was absent; whilst in the trigone the effects of cromakalim were similar in mucosa-intact and denuded strips. Upon examination of the strips of mucosa by immunofluorescence these strips were shown to contain cells positive for alpha-SMA or vimentin and cells positive for both, suggesting the presence of not only urothelium but also suburothelium and some detrusor smooth muscle bundles. In the dome, the urothelium and suburothelium reduce the inhibitory effect of cromakalim on spontaneous contractions, whilst in the trigone these structures appear to have little influence. The mechanism for generating spontaneous contractions in the intact strips seems to be linked to the urothelium and suburothelium in the dome but not in the trigone.