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 Ca2+ oscillations in smooth muscle cells from pathologically overactive human bladders. Basal cytoplasmic Ca2+ concentration was elevated in smooth muscle cells from overactive bladders. Unprovoked, spontaneous rises of Ca2+ were also identified. These spontaneous Ca2+ oscillations were Ca2+-dependent, sensitive to L-type Ca2+ channel antagonist verapamil and also attenuated by blocking SR Ca2+ reuptake. The fraction of spontaneously active cells was higher in cells from overactive bladders and the magnitude of spontaneous Ca2+ oscillations also greater. Spontaneous action potentials or depolarising oscillations were also observed, associated with Ca2+ rise; with a higher percentage of cells from idiopathic OAB, but not in neurogenic OAB. Low concentrations of NiCl2 attenuated both spontaneous electrical and Ca2+ activation. This study provides the first evidence that spontaneous, autonomous cellular activity-Ca2+ and membrane potential oscillations, originates from detrusor smooth muscle in human bladders, mediated by extracellular Ca2+ influx and intracellular release. Such cellular activity underlies spontaneous muscle contraction and defective Ca2+ activation contributes to up-regulated contractile activity in overactive bladders. (C) 2009 Elsevier Ltd. All rights reserved.