ATP transients accompany spontaneous contractions in isolated guinea-pig detrusor smooth muscle

Spontaneous contractions are characteristic of the bladder wall, but their origins remain unclear. Activity is reduced if the mucosa is removed but does not disappear, suggesting a fraction arises from the detrusor. We tested the hypothesis that spontaneous detrusor contractions arise from spontaneous ATP release. Guinea-pig detrusor strips, without mucosa, were superfused with Tyrode’s solution at 36°C. Preparations were electrically field stimulated (EFS, 3-sec trains at 90-second intervals) to produce nerve-mediated contractions, abolished by 1 µM tetrodotoxin. Amperometric ATP electrodes on the preparation surface recorded any released ATP. Spontaneous contractions and ATP transients were recorded between EFS stimulation. Nerve-mediated contractions were attenuated by atropine and  methylene ATP: in combination they nearly abolished contractions, as did nifedipine. Contractions were accompanied by ATP transients that were unaffected by atropine but inhibited by TTX and greatly attenuated by nifedipine. Spontaneous contractions were accompanied by ATP transients with a close correlation between the magnitudes of both transients. ATP and contractile transients persisted with TTX, atropine and nifedipine. Immediately after a nerve-mediated contraction and ATP transient there was a longer interval than normal before spontaneous activity resumed. Spontaneous contractions and ATP transients are proposed to arise from ATP leakage from nerve terminals innervating the detrusor. Extracellular ATP has a greater functional significance in humans who suffer from detrusor overactivity (spontaneous bladder contractions associated with incontinence) due to its reduced hydrolysis at the nerve-muscle interface. This study shows the origin of spontaneous activity that may be exploited to develop a therapeutic management of this condition.