Ca2+ regulation in detrusor smooth muscle from ovine fetal bladder after in utero bladder outflow obstruction.
776 - 780.
Purpose: We characterized intracellular Ca2+ regulation in fetal bladders following outflow obstruction by examining the Ca2+ response to agonists in smooth muscle cells.Materials and Methods: Severe bladder outflow obstruction was induced in male fetal sheep by placing a urethral ring and urachal ligation midway through gestation at 75 days. Fetuses were examined 30 days after surgery. Intracellular Ca2+ in single smooth muscle cells isolated from the bladder wall was measured with epifluorescence microscopy using fura-2(AM) during exposure to agonists, such as carbachol and adenosine triphosphate, and to other activators, such as caffeine and KCI.Results: Detrusor smooth muscle cells from obstructed bladders had resting intracellular Ca2+ similar to that in sham operated controls. The maximal response to carbachol was decreased following obstruction (p < 0.05). Construction of dose-response curves also demonstrated higher EC50 (p < 0.05). However, these changes were not mirrored by caffeine evoked Ca2+ release, which was not significantly different between the obstruction group and sham operated controls. Kinetic analysis of carbachol transients further revealed an attenuated maximal rate of increase in obstructed bladders (p < 0.01). The magnitude of intracellular Ca2+ to purinergic neurotransmitter adenosine triphosphate was also found to be smaller in cells from obstructed bladders (p < 0.05), although transmembrane influx by high K depolarization was not significantly affected.Conclusions: Muscarinic and purinergic pathways were down-regulated in fetal detrusor muscle following outflow obstruction. These major functional receptors appeared to be more susceptible to obstruction than other Ca2+ regulators. Their impairment may contribute to the compromised contractile function seen in in utero bladder outflow obstruction.
|Title:||Ca2+ regulation in detrusor smooth muscle from ovine fetal bladder after in utero bladder outflow obstruction|
|Keywords:||bladder, muscle, smooth, bladder neck obstruction, sheep, calcium, POSTERIOR URETHRAL VALVES, OUTLET OBSTRUCTION, URINARY-BLADDER, EXPRESSION, RATS, RECEPTORS, CHILDREN, RABBIT|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health
Archive Staff Only