Aberrant Ca2+ oscillations in smooth muscle cells from overactive human bladders.

Overactive bladder (OAB) syndrome is highly prevalent and costly, but its pathogenesis remains unclear; in particular, the origin of involuntary detrusor muscle activity. To identify the functional substrate for detrusor muscle overactivity, we examined intracellular Ca(2+) oscillations in smooth muscle cells from pathologically overactive human bladders. Basal cytoplasmic Ca(2+) concentration was elevated in smooth muscle cells from overactive bladders. Unprovoked, spontaneous rises of Ca(2+) were also identified. These spontaneous Ca(2+) oscillations were Ca(2+)-dependent, sensitive to L-type Ca(2+) channel antagonist verapamil and also attenuated by blocking SR Ca(2+) reuptake. The fraction of spontaneously active cells was higher in cells from overactive bladders and the magnitude of spontaneous Ca(2+) oscillations also greater. Spontaneous action potentials or depolarising oscillations were also observed, associated with Ca(2+) rise; with a higher percentage of cells from idiopathic OAB, but not in neurogenic OAB. Low concentrations of NiCl(2) attenuated both spontaneous electrical and Ca(2+) activation. This study provides the first evidence that spontaneous, autonomous cellular activity-Ca(2+) and membrane potential oscillations, originates from detrusor smooth muscle in human bladders, mediated by extracellular Ca(2+) influx and intracellular release. Such cellular activity underlies spontaneous muscle contraction and defective Ca(2+) activation contributes to up-regulated contractile activity in overactive bladders.