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.
Institute of Urology, University College London, UK.
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Sui
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Fry
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Malone-Lee
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Wu
D000328:Adult; D000368:Aged; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D053201:Urinary Bladder, Overactive / Q000378:metabolism* / Q000503:physiopathology
D020747:Calcium Channels, T-Type; D002118:Calcium