Premium
Control of Ins P 3 ‐induced Ca 2+ oscillations in permeabilized blowfly salivary gland cells: contribution of mitochondria
Author(s) -
Zimmermann Bernhard
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.t01-1-00707.x
Subject(s) - oligomycin , biophysics , cyclopiazonic acid , calcium , cytosol , ruthenium red , mitochondrion , membrane potential , intracellular , inositol , chemistry , fura 2 , biology , biochemistry , receptor , atpase , organic chemistry , enzyme
1 Many agonists linked to the generation of inositol 1,4,5‐trisphosphate (Ins P 3 ) and release of Ca 2+ from intracellular stores induce repetitive transients in cytosolic Ca 2+ whose frequency increases over a certain range of agonist concentrations. 2 In order to investigate the mechanisms underlying this frequency modulation, the fluorescent Ca 2+ sensor mag‐fura‐2 was loaded into intracellular calcium stores and used to monitor Ins P 3 ‐induced dynamics of the intraluminal calcium concentration ([Ca 2+ ] L ) in secretory cells of permeabilized blowfly Calliphora vicina salivary glands. 3 In this preparation, increasing concentrations of Ins P 3 induced graded decreases in [Ca 2+ ] L that were often superimposed with repetitive [Ca 2+ ] L transients produced by sequential Ca 2+ release and re‐uptake. These [Ca 2+ ] L oscillations developed at frequencies of 3–11 min −1 unrelated to the concentration of Ins P 3 present. 4 In contrast, incremental concentrations of Ins P 3 applied in the presence of the oxidizable mitochondrial substrates citrate, succinate, or pyruvate‐malate induced repetitive [Ca 2+ ] L transients whose frequency increased with the concentration of Ins P 3 . 5 This Ins P 3 concentration‐dependent modulation of oscillation frequency was abolished after dissipating the mitochondrial membrane potential (Δψ m ) by combined treatment with carbonyl cyanide p‐ trifluoromethoxyphenyl hydrazone + oligomycin or after application of Ruthenium Red, an inhibitor of mitochondrial Ca 2+ uptake. 6 Taken together, the data indicate that energized mitochondria exert negative control over the frequency of Ins P 3 ‐induced Ca 2+ oscillations. It is concluded that mitochondria play a crucial role in determining the duration of the interspike period and, therefore, for the encoding of amplitude‐modulated, Ins P 3 ‐liberating stimuli into the frequency of cytosolic Ca 2+ oscillations.