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Highly supralinear feedback inhibition of Ca2+ uptake by the Ca2+ load of intracellular stores

Authors
Favre, C. J.
Jacquet, J.
Published in Journal of Biological Chemistry. 1996, vol. 271, no. 25, p. 14925-14930
Abstract Net Ca2+ uptake into intracellular Ca2+ stores of homogenized cells is transient, even when the extravesicular Ca2+ concentration is kept constant. To study the mechanism underlying the phenomenon, we have investigated 45Ca2+ uptake by HL-60 cell homogenates. The initial rate of Ca2+ uptake as well as the final amount of stored Ca2+ were a function of the extravesicular Ca2+ concentration. However, Ca2+ uptake stopped independently of the extravesicular Ca2+ concentration after approximately 10 min. Studies using Ca2+-ATPase inhibitors demonstrated that the transient nature of the net uptake was not due to Ca2+ efflux. Monovalent cation ionophores did not influence the Ca2+ uptake curves, excluding a relevant involvement of pH and membrane potential. Together with the observation of a continued Ca2+ uptake in the presence of the intralumenal Ca2+ chelator oxalate, these results strongly suggest a feedback inhibition of Ca2+ uptake by the Ca2+ load of intracellular stores. The concentration-inhibition relationship between the Ca2+ load and the rate of Ca2+ uptake was highly supralinear (slope factor >/= 4). IC50 and maximum of the dose-inhibition curve, but not the slope factor were a function of the extravesicular free Ca2+ concentration. A series of three logistic equations derived from our data allowed an appropriate description of the behavior of Ca2+ uptake. Our results suggest, in addition to its well known activation by cytosolic Ca2+ concentration, a highly supralinear feedback inhibition of Ca2+ uptake by the Ca2+ load of intracellular stores. The steepness of the feedback inhibition might have a profound effect on spatial and temporal behavior of the Ca2+ signal.
Keywords Biological Transport/drug effectsCalcium/ metabolismCalcium RadioisotopesCalcium-Transporting ATPases/antagonists & inhibitorsCell-Free SystemChelating Agents/pharmacologyEnzyme Inhibitors/pharmacologyFeedbackGramicidin/pharmacologyHL-60 CellsHumansKineticsMathematicsModels, TheoreticalMonensin/pharmacologyNigericin/pharmacologyOxalates/pharmacologyValinomycin/pharmacology
Identifiers
PMID: 8662967
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Other version: http://www.jbc.org/content/271/25/14925.full.pdf
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FAVRE, C. J. et al. Highly supralinear feedback inhibition of Ca2+ uptake by the Ca2+ load of intracellular stores. In: Journal of Biological Chemistry, 1996, vol. 271, n° 25, p. 14925-14930. https://archive-ouverte.unige.ch/unige:7204

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Deposited on : 2010-06-21

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