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      Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria.

      Science (New York, N.Y.)

      Aequorin, metabolism, Calcium, Cell Membrane Permeability, physiology, HeLa Cells, Histamine, pharmacology, Humans, Inositol 1,4,5-Trisphosphate, Mitochondria, drug effects, Osmolar Concentration, Recombinant Fusion Proteins

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          Abstract

          Microdomains of high intracellular calcium ion concentration, [Ca2+]i, have been hypothesized to occur in living cells exposed to stimuli that generate inositol 1,4,5-trisphosphate (IP3). Mitochondrially targeted recombinant aequorin was used to show that IP3-induced Ca2+ mobilization from intracellular stores caused increases of mitochondrial Ca2+ concentration, [Ca2+]m, the speed and amplitude of which are not accounted for by the relatively small increases in mean [Ca2+]i. A similar response was obtained by the addition of IP3 to permeabilized cells but not by perfusion of cells with Ca2+ at concentrations similar to those measured in intact cells. It is concluded that in vivo, domains of high [Ca2+]i are transiently generated close to IP3-gated channels and sensed by nearby mitochondria; this may provide an efficient mechanism for optimizing mitochondrial activity upon cell stimulation.

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          8235595

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