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

Sui, G, Fry, CH, Malone-Lee, J and Wu, C (2009) Aberrant Ca2+ oscillations in smooth muscle cells from overactive human bladders CELL CALCIUM, 45 (5). 456 - 464. ISSN 0143-4160

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Abstract

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.

Item Type: Article
Additional Information: NOTICE: this is the author’s version of a work that was accepted for publication in Cell Calcium. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cell Calcium, 45(5), May 2009, DOI 10.1016/j.ceca.2009.03.001.
Uncontrolled Keywords: Human detrusor, Spontaneous activity, Intracellular Ca2+, Overactive bladders, L-type Ca2+ channel, T-type Ca2+ channel, GUINEA-PIG BLADDER, IDIOPATHIC DETRUSOR INSTABILITY, INTRACELLULAR CA2+, URINARY-BLADDER, INTERSTITIAL-CELLS, OUTLET OBSTRUCTION, HEART-FAILURE, PATHOPHYSIOLOGY, CALCIUM, CHANNELS
Divisions: Faculty of Health and Medical Sciences > Clinical Medicine
Depositing User: Symplectic Elements
Date Deposited: 02 Dec 2011 11:54
Last Modified: 23 Sep 2013 18:53
URI: http://epubs.surrey.ac.uk/id/eprint/25595

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