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

K.D. McCloskey, U.A. Anderson, R.A. Davidson, Y.R. Bayguinov, K.M. Sanders, S.M. Ward

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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.
Original languageEnglish
Pages (from-to)273-283
Number of pages10
JournalBritish Journal of Pharmacology
Volume156
Issue number2
DOIs
Publication statusPublished - Jan 2009

Keywords

  • interstitial cells
  • nerve-mediated contraction
  • immunohistochemistry
  • intracellular recordings

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