title: Cytosolic Ca(2+) and Ca(2+)-activated Cl(-) current dynamics: insights from two functionally distinct mouse exocrine cells.
abstract: The dynamics of Ca(2+) release and Ca(2+)-activated Cl(-) currents in two related, but functionally distinct exocrine cells, were studied to gain insight into how the molecular specialization of Ca(2+) signalling machinery are utilized to produce different physiological endpoints: in this case, fluid or exocytotic secretion. Digital imaging and patch-clamp methods were used to monitor the temporal and spatial properties of changes in cytosolic Ca(2+) concentration ([Ca(2+)](c)) and Cl(-) currents following the controlled photolytic release of caged-InsP(3) or caged-Ca(2+). In parotid and pancreatic acinar cells, changes in [Ca(2+)](c) and activation of a Ca(2+)-activated Cl(-) current occurred with close temporal coincidence. In parotid, a rapid global Ca(2+) signal was invariably induced, even with low-level photolytic release of threshold amounts of InsP(3). In pancreas, threshold stimulation generated an apically delimited [Ca(2+)](c) signal, while a stronger stimulus induced a global [Ca(2+)](c) signal which exhibited characteristics of a propagating wave. InsP(3) was more effective in parotid, where [Ca(2+)](c) signals initiated with shorter latency and exhibited a faster time-to-peak than in pancreas. The increased potency of InsP(3) in parotid probably results from a four-fold higher number of InsP(3) receptors as measured by radiolabelled InsP(3) binding and western blot analysis. The Ca(2+) sensitivity of the Cl(-) channels in parotid and pancreas was determined from the [Ca(2+)]-current relationship measured during a dynamic 'Ca(2+) ramp' produced by the continuous, low-level photolysis of caged-Ca(2+). In addition to a greater number of InsP(3) receptors, the Cl(-) current density of parotid acinar cells was more than four-fold greater than that of pancreatic cells. Whereas activation of the current was tightly coupled to increases in Ca(2+) in both cell types, local Ca(2+) clearance was found to contribute substantially to the deactivation of the current in parotid. These data reveal specializations of common modules of Ca(2+)-release machinery and subsequent effector activation that are specifically suited to the distinct functional roles of these two related cell types.
authors.affiliation: Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Giovannucci
authors.forename: Jason I E
authors.initials: JI
authors.lastname: Bruce
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Straub
authors.forename: Jorge
authors.initials: J
authors.lastname: Arreola
authors.forename: James
authors.initials: J
authors.lastname: Sneyd
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Shuttleworth
authors.forename: David I
authors.initials: DI
authors.lastname: Yule
mesh_terms: D000465:Algorithms; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism*; D004558:Electric Stimulation; D004594:Electrophysiology; D007091:Image Processing, Computer-Assisted; D007293:Inosine Triphosphate / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010306:Parotid Gland / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010782:Photolysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D018118:Chloride Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D007293:Inosine Triphosphate