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Mitochondria regulate Ca 2+ wave initiation and inositol trisphosphate signal transduction in oligodendrocyte progenitors
Author(s) -
Haak Laurel L.,
Grimaldi Maurizio,
Smaili Soraya S.,
Russell James T.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.0022-3042.2001.00727.x
Subject(s) - mitochondrion , inositol , inositol trisphosphate , microbiology and biotechnology , cytosol , biophysics , phospholipase c , inositol trisphosphate receptor , calcium signaling , biology , chemistry , biochemistry , signal transduction , receptor , enzyme
Mitochondria in oligodendrocyte progenitor cells (OPs) take up and release cytosolic Ca 2+ during agonist‐evoked Ca 2+ waves, but it is not clear whether or how they regulate Ca 2+ signaling in OPs. We asked whether mitochondria play an active role during agonist‐evoked Ca 2+ release from intracellular stores. Ca 2+ puffs, wave initiation, and wave propagation were measured in fluo‐4 loaded OP processes using linescan confocal microscopy. Mitochondrial depolarization, measured by tetramethyl rhodamine ethyl ester (TMRE) fluorescence, accompanied Ca 2+ puffs and waves. In addition, waves initiated only where mitochondria were localized. To determine whether energized mitochondria were necessary for wave generation, we blocked mitochondrial function with the electron transport chain inhibitor antimycin A (AA) in combination with oligomycin. AA decreased wave speed and puff probability. These effects were not due to global changes in ATP. We found that AA increased cytosolic Ca 2+ , markedly reduced agonist‐evoked inositol trisphosphate (IP 3 ) production, and also enhanced phosphatidylinositol 4,5‐bisphosphate (PIP2) binding to the Ca 2+ dependent protein gelsolin. Thus, the reduction in puff probability and wave speed after AA treatment may be explained by competition for PIP 2 between phospholipase C and gelsolin. Energized mitochondria and low cytosolic Ca 2+ concentration may be required to maintain PIP2, a substrate for IP 3 signal transduction.