title: Intracellular Ca(2+) regulation and electrophysiolgical properties of bladder urothelium subjected to stretch and exogenous agonists.
abstract: Intracellular Ca(2+) control and the electrophysiological properties of guinea-pig urothelium were measured during interventions encountered during bladder filling, including cell stretch and exposure to exogenous transmitters such as ATP and muscarinic agonists. Stretch, achieved by exposure to solutions of altered osmolality, generated intracellular Ca(2+)-transients that were attenuated by Gd(3+) in isolated cells. However ATP-induced intracellular Ca(2+)-transients were unaffected by Gd(3+) but blocked by thapsigargin. ATP-dependent Ca(2+)-transients were followed by a large inward current at a holding potential of -60mV. Carbachol was without significant effect, except for a small slowing of the rate of spontaneous intracellular Ca(2+)-transients that were recorded in about one-third of cells. With urothelial sheets the transepithelial potential (TEP) was increased by ATP applied to the baso-lateral (serosal) face, a similar change was achieved by reduction of the basolateral [Na]; carbachol was without significant effect. We propose that a rise of intracellular Ca(2+) may control ATP release as both mechanical stretch and exogenous ATP have been shown previously to release further ATP from isolated urothelium as part of a postulated signalling pathway for bladder filling. The similar increase of TEP by ATP and a raised transepithelial Na gradient is also consistent with a role for transepithelial ion transport as a regulator of ATP release. The lack of large effects with carbachol implies muscarinic agonists must exert any effects on the urothelium through other pathways.
authors.affiliation: Postgraduate Medical School, University of Surrey, Guildford GU2 7WG, UK.
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.forename: G P
authors.initials: GP
authors.lastname: Gui
authors.forename: C H
authors.initials: CH
authors.lastname: Fry
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D005682:Gadolinium / Q000494:pharmacology; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000502:physiology; D009994:Osmolar Concentration; D012964:Sodium / Q000494:pharmacology; D013314:Stress, Mechanical; D019284:Thapsigargin / Q000494:pharmacology; D001743:Urinary Bladder / Q000166:cytology; D019459:Urothelium / Q000187:drug effects / Q000502:physiology*
chemical_list: D019284:Thapsigargin; D000255:Adenosine Triphosphate; D002217:Carbachol; D012964:Sodium; D005682:Gadolinium; D002118:Calcium