Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice.
OBJECTIVE
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).


METHODS
Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.


RESULTS
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.


CONCLUSIONS
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.
McCloskey
K D
KD
Physiology, Division of Basic Medical Sciences, Medical Biology Centre, 97 Lisburn Road, Belfast, Northern Ireland, UK. k.mccloskey@qub.ac.uk
Anderson
U A
UA
Davidson
R A
RA
Bayguinov
Y R
YR
Sanders
K M
KM
Ward
S M
SM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D013045:Species Specificity; D013779:Tetrodotoxin / Q000494:pharmacology; D015854:Up-Regulation; D001743:Urinary Bladder / Q000166:cytology / Q000502:physiology*; D014746:Vimentin / Q000378:metabolism
D014746:Vimentin; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D013779:Tetrodotoxin; D011732:Pyridoxal Phosphate; D001285:Atropine; D019009:Proto-Oncogene Proteins c-kit