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NEUROREGULATION AND MOTILITY
Departments of 1Anatomy and Neurobiology and 2Pharmacology, University of Vermont College of Medicine, Burlington, Vermont
Submitted 14 September 2007 ; accepted in final form 27 November 2007
Mitochondrial Ca2+ handling has been implicated in spontaneous rhythmic activity in smooth muscle and interstitial cells of Cajal. In this investigation we evaluated the effect of mitochondrial inhibitors on spontaneous action potentials (APs), Ca2+ flashes, and Ca2+ waves in gallbladder smooth muscle (GBSM). Disruption of the mitochondrial membrane potential with carbonyl cyanide 3-chlorophenylhydrazone, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone, rotenone, and antimycin A significantly reduced or eliminated APs, Ca2+ flashes, and Ca2+ waves in GBSM. Blockade of ATP production with oligomycin did not alter APs or Ca2+ flashes but significantly reduced Ca2+ wave frequency. Inhibition of mitochondrial Ca2+ uptake and Ca2+ release with Ru360 and CGP-37157, respectively, reduced the frequency of Ca2+ flashes and Ca2+ waves in GBSM. Similar to oligomycin, cyclosporin A did not alter AP and Ca2+ flash frequency but significantly reduced Ca2+ wave activity. These data suggest that mitochondrial Ca2+ handling is necessary for the generation of spontaneous electrical activity and may therefore play an important role in gallbladder tone and motility.
motility; sarcoplasmic reticulum; calcium transients; slow waves; action potentials
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