Title:
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Interstitial cells of the lower urinary tract
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The aims of the present study were to characterise the location and morphology of ICC in the
urethra and bladder and to examine their structural relationships with nerves and smooth muscle.
Also, to investigate the physiological role of ICC in the normal bladder by investigating the Ca2+
signalling in smooth muscle cells and ICC, in in situ mucosal preparations of guinea pig bladder,
using ca2+~imaging techniques.
Rabbit urethras were fixed, labelled with antibodies and examined with confocal microscopy.
Staining with Masson's Trichrome showed the arrangement of smooth muscle bundles into distinct
layers. Anti-c-kit revealed a population of immuno-positive ICC, which were either elongated with
several lateral branches or stellate with branches coming from a central soma. ICC were found
throughout the muscularis. c-kit-positive ICC were found on the boundary of the myosin-positive
smooth muscle bundles, and also in the spaces between. Anti-c-kit and anti-neurofilament showed
frequent points of close contact between the c-kit-positive ICC and nerves some of which were
immunopositive for nNos.
Spontaneous Ca2+ transients were investigated within the live guinea pig bladder using Oregon green
Ca2+ indicator. Spontaneous smooth muscle Ca2+ transients took two forms, uncoordintated single
cell Ca2+ events, and coordinated whole bundle flashes. ICC generated Ca2+ transients had longer
durations and were significantly less frequent than smooth muscle cell events. There was little
evidence of correlation between the spontaneous Ca2+ transients of smooth muscle cells and those
of ICC. Both the smooth muscle cell and ICC activity were affected by various store and channel
blockers. In conclusion, ICC were located throughout the wall of the rabbit urethra, where they came into
close contact with smooth muscle cells and nerves. ICC could have a role in the excitation of
smooth muscle cells in the urinary bladder, providing a possible therapeutic target for many
urinary tract pathologies.
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