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Cyclopiazonic acid depletes intracellular Ca2+ stores and activates an influx pathway for divalent cations in HL-60 cells

Published in Journal of Biological Chemistry. 1992, vol. 267, no. 4, p. 2318-2324
Abstract The filling state of intracellular Ca2+ stores has been proposed to regulate Ca2+ influx across the plasma membrane in a variety of tissues. To test this hypothesis, we have used three structurally unrelated inhibitors of the Ca(2+)-ATPase of intracellular Ca2+ stores and investigated their effect on Ca2+ homeostasis in HL-60 cells. Without increasing cellular inositol (1,4,5)trisphosphate levels, all three inhibitors (cyclopiazonic acid, thapsigargin, and 2,5-Di-tert-butylhydroquinone) released Ca2+ from intracellular stores, resulting in total depletion of agonist-sensitive Ca2+ stores. The Ca2+ release was relatively slow with a lag time of 5 s and a time to peak of 60 s. After a lag time of approximately 15 s, all three Ca(2+)-ATPase inhibitors activated a pathway for divalent cation influx across the plasma membrane. At a given concentration of an inhibitor, the plasma membrane permeability for divalent cations closely correlated with the extent of depletion of Ca2+ stores. The influx pathway activated by Ca(2+)-ATPase inhibitors conducted Ca2+, Mn2+, Co2+, Zn2+, and Ba2+ and was blocked, at similar concentrations, by La3+, Ni2+, Cd2+, as well as by the imidazole derivate SK&F 96365. The divalent cation influx in response to the chemotactic peptide fMLP had the same characteristics, suggesting a common pathway for Ca2+ entry. Our results support the idea that the filling state of intracellular Ca2+ stores regulates Ca2+ influx in HL-60 cells.
Keywords Biological TransportCalcium/ metabolismCalcium-Transporting ATPases/antagonists & inhibitorsCations, Divalent/metabolismCell LineCell Membrane Permeability/drug effectsFura-2Hydroquinones/pharmacologyImidazoles/pharmacologyIndoles/ pharmacologyMycotoxins/toxicityN-Formylmethionine Leucyl-Phenylalanine/pharmacologyTerpenes/pharmacologyThapsigargin
PMID: 1531138
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DEMAUREX, Nicolas, LEW, Daniel Pablo, KRAUSE, Karl-Heinz. Cyclopiazonic acid depletes intracellular Ca2+ stores and activates an influx pathway for divalent cations in HL-60 cells. In: Journal of Biological Chemistry, 1992, vol. 267, n° 4, p. 2318-2324. https://archive-ouverte.unige.ch/unige:7164

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Deposited on : 2010-06-21

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