Abstract
IN many cell types, receptor-mediated Ca2+ release from internal stores is followed by Ca2+ influx across the plasma membrane1–3. The sustained entry of Ca2+ is thought to result partly from the depletion of intracellular Ca2+ pools4,5. Most investigations have characterized Ca2+ influx indirectly by measuring Ca2+-activated currents6–9 or using Fura-2 quenching by Mn2, which in some cells enters the cells by the same influx pathway10,11. But only a few studies have investigated this Ca2+ entry pathway more directly12–14. We have combined patch-clamp and Fura-2 measurements to monitor membrane currents in mast cells under conditions where intracellular Ca2+ stores were emptied by either inositol 1,4,5-trisphosphate, ionomycin, or excess of the Ca2+ chelator EGTA. The depletion of Ca2+ pools by these independent mechanisms commonly induced activation of a sustained calcium inward current that was highly selective for Ca2+ ions over Ba2+, Sr2+ and Mn2+. This Ca2+ current, which we termICRAC (calcium release-activated calcium), is not voltage-activated and shows a characteristic inward rectification. It may be the mechanism by which electrically nonexcitable cells maintain raised intracellular Ca2+ concentrations and replenish their empty Ca2+ stores after receptor stimulation.
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Hoth, M., Penner, R. Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature 355, 353–356 (1992). https://doi.org/10.1038/355353a0
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DOI: https://doi.org/10.1038/355353a0
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