Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice |
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Authors: | KD McCloskey UA Anderson RA Davidson YR Bayguinov KM Sanders SM Ward |
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Affiliation: | 1.Physiology, Division of Basic Medical Sciences, Medical Biology Centre, Belfast, UK;2.Centre for Biophotonics, University of Strathclyde, Glasgow, UK;3.Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, NV, USA |
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Abstract: | Background and purpose:W/Wv and wild-type murine bladders were studied to determine whether the W/Wv phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).Experimental approach:Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.Key results:Wild-type and W/Wv detrusors contained c-Kit- and vimentin-immunopositive cells in comparable quantities, distribution and morphology. Electrical field stimulation evoked tetrodotoxin-sensitive contractions in wild-type and W/Wv detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25% reduction occurred in W/Wv strips. The atropine-insensitive component was blocked by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both tissue types. Wild-type and W/Wv detrusors had similar resting membrane potentials of −48 mV. Spontaneous electrical activity in both tissue types comprised action potentials and unitary potentials. Action potentials were nifedipine-sensitive whereas unitary potentials were not. Excitatory junction potentials were evoked by single pulses in both tissues. These were reduced by atropine in wild-type tissues but not in W/Wv preparations. The atropine-insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both preparations.Conclusions and implications:Bladders from W/Wv mice contain c-Kit- and vimentin-immunopositive ICC. There are similarities in the electrical and contractile properties of W/Wv and wild-type detrusors. However, significant differences were found in the pharmacology of the responses to neurogenic stimulation with an apparent up-regulation of the purinergic component. These findings indicate that the W/Wv strain may not be the best model to study ICC function in the bladder. |
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Keywords: | Interstitial cells nerve-mediated contraction immunohistochemistry intracellular recordings |
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