MICRODOMAINS WITH HIGH CA2-SENSITIVE CHANNELS THAT ARE SENSED BY NEIGHBORING MITOCHONDRIA( CLOSE TO IP(3))

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