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Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/W-v mice

McCloskey, K.D. and Anderson, U.A. and Davidson, R.A. and Bayguinov, Y.R. and Sanders, K.M. and Ward, S.M. (2009) Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/W-v mice. British Journal of Pharmacology, 156 (2). pp. 273-283. ISSN 0007-1188

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Abstract

W/W-v and wild-type murine bladders were studied to determine whether the W/W-v 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). Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders. Wild-type and W/W-v 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/W-v detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25% reduction occurred in W/W-v 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/W-v 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/W-v preparations. The atropine-insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid in both preparations. Bladders from W/W-v mice contain c-Kit- and vimentin-immunopositive ICC. There are similarities in the electrical and contractile properties of W/W-v 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/W-v strain may not be the best model to study ICC function in the bladder.