title: Evidence for a direct inhibitory effect of extracellular H+ on store depletion-activated Ca2+ entry in vascular endothelial cells.
abstract: Modulation of store depletion-activated Ca2+ entry by acidosis was investigated in ECV304 endothelial cells. Lowering extracellular pH from 7.4 to 6.9 markedly suppressed Ca2+ entry elicited by direct depletion of Ca2+ stores with thapsigargin (100 nM), but did not significantly affect leak Ca2+ entry. Acidosis diminished thapsigargin-induced Ca2+ entry by 53.7 +/- 7.8% at 2.5 mM extracellular Ca2+. A similar degree of inhibition was observed in cells depolarized by high extracellular K+ (100 mM). Reduction of extracellular pH from 7.4 to 6.9 was associated with a decrease in intracellular pH from 7.23 +/- 0.01 to 7.01 +/- 0.03. Propionate (20 mM) caused a reduction of intracellular pH to 6.97 +/- 0.02, but failed to suppress store depletion-activated Ca2+ entry at 2.5 mM extracellular Ca2+ significantly. Our results suggest that an increase in extracellular proton concentration inhibits store depletion-activated Ca2+ entry through a direct, membrane potential-independent effect on the plasmalemmal Ca2+ channel.
authors.affiliation: Institut Für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Wakabayashi
authors.forename: K
authors.initials: K
authors.lastname: Groschner
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D011188:Potassium / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
chemical_list: D013729:Terpenes; D019284:Thapsigargin; D006859:Hydrogen; D011188:Potassium; D002118:Calcium