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Title: Functional innervation and neurogenic dependence of interstitial cells in the urinary bladder
Author: Gray , Susannah Mary Yvette
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
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Interstitial cells of Caja l (ICC) are found throughout the bladder wall as distinct sub-populations: interconnected networks of stellate ICC-LP in the lamina propria, intramuscular ICC-1M which are elongated with branched processes tracking smooth muscle bundles and interbundle ICC-lB. Patterns of electrical and Ca 2+-signalling are distinctly different between ICC and smooth muscle cells (SMC). Immunofluorescence and electron microscopy show the proximity of ICC-LP and ICC- 1M to nerves; moreover ICC respond to exogenous agonists by firing Ca2+ transients or electrical currents. In the present study, guinea-pig bladder ICC sub-populations exhibited distinctive patterns of spontaneous Ca 2+-s ignalling. ICC-1M activity was apparently not correlated with signalling in neighbouring SMC. In the lamina propria, Ca2+-transients propagated from one ICC-LP to another, indicating that lCC-LP comprise a functional network. Spontaneous activity in perivascular ICC (P ICC) and vascular smooth muscle (VSM) from suburothelial microvessels is reported for the first time. Neurogenic stimulation via electrical field stimulation (EFS) evoked Ca2+-transients in all cell populations. Asynchronous activity in ICC-1M and SMC was coordinated by EFS. ICC-LP, which were poorly synchronised pre-stimulation, responded to EFS with coordinated Ca2+-transients. PICC and VSM also responded synchronously to neurogenic stimulation. These novel findings demonstrate that bladder ICC are functionally innervated, and implicate ICC in neurogenic modulation of bladder function. A time-dependent study assessing changes to interstitial cells (IC) in the neurogenic spinal cord injured bladder was carried out. Early reduction in vimentin+ and PDGFRa+ IC was associated with apoptosis, necrosis, and autophagy, which was followed by proliferation and a new steady state. Lesions in IC were associated with a loss of nerve fibres throughout the detrusor, and smooth muscle hypertrophy which correlated with dysfunctional bladder activity. In summary, the findings of the present study demonstrate for the first time that bladder ICC are functionally innervated and furthermore reveals their neurogenic dependence in normal physiology.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available