title: Effect of intracellular pH on acetylcholine-induced Ca2+ waves in mouse pancreatic acinar cells.
abstract: We have used fluo 3-loaded mouse pancreatic acinar cells to investigate the relationship between Ca2+ mobilization and intracellular pH (pHi). The Ca2+-mobilizing agonist ACh (500 nM) induced a Ca2+ release in the luminal cell pole followed by spreading of the Ca2+ signal toward the basolateral side with a mean speed of 16.1 +/- 0.3 micron/s. In the presence of an acidic pHi, achieved by blockade of the Na+/H+ exchanger or by incubation of the cells in a Na+-free buffer, a slower spreading of ACh-evoked Ca2+ waves was observed (7.2 +/- 0.6 micron/s and 7.5 +/- 0.3 micron/s, respectively). The effects of cytosolic acidification on the propagation rate of ACh-evoked Ca2+ waves were largely reversible and were not dependent on the presence of extracellular Ca2+. A reduction in the spreading speed of Ca2+ waves could also be observed by inhibition of the vacuolar H+-ATPase with bafilomycin A1 (11.1 +/- 0.6 micron/s), which did not lead to cytosolic acidification. In contrast, inhibition of the endoplasmic reticulum Ca2+-ATPase by 2,5-di-tert-butylhydroquinone led to faster spreading of the ACh-evoked Ca2+ signals (25.6 +/- 1.8 micron/s), which was also reduced by cytosolic acidification or treatment of the cells with bafilomycin A1. Cytosolic alkalinization had no effect on the spreading speed of the Ca2+ signals. The data suggest that the propagation rate of ACh-induced Ca2+ waves is decreased by inhibition of Ca2+ release from intracellular stores due to cytosolic acidification or to Ca2+ pool alkalinization and/or to a decrease in the proton gradient directed from the inositol 1,4, 5-trisphosphate-sensitive Ca2+ pool to the cytosol.
authors.affiliation: Department of Physiology II, University of Saarland, D-66421 Homburg/Saar, Germany.
authors.forename: A
authors.initials: A
authors.lastname: González
authors.forename: F
authors.initials: F
authors.lastname: Pfeiffer
authors.forename: A
authors.initials: A
authors.lastname: Schmid
authors.forename: I
authors.initials: I
authors.lastname: Schulz
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006873:Hydroquinones / Q000494:pharmacology; D007424:Intracellular Fluid / Q000502:physiology; D007700:Kinetics; D018942:Macrolides; D008297:Male; D008536:Meglumine / Q000494:pharmacology; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D012430:Ruthenium Red / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D018942:Macrolides; D012430:Ruthenium Red; D008536:Meglumine; C040929:bafilomycin A1; C018855:2-tert-butylhydroquinone; D006180:Proton-Translocating ATPases; D000252:Calcium-Transporting ATPases; D000109:Acetylcholine; D002118:Calcium