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Mitochondrial calcium sequestration and protein kinase C cooperate in the regulation of cortical F‐actin disassembly and secretion in bovine chromaffin cells
Author(s) -
CuchilloIbáñez I.,
Lejen T.,
Albillos A.,
Rosé S. D.,
Olivares R.,
Villarroya M.,
García A. G.,
Trifaró J.M.
Publication year - 2004
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 - 10.1113/jphysiol.2004.064063
Subject(s) - chelerythrine , cytochalasin d , protein kinase c , microbiology and biotechnology , staurosporine , biology , actin , mitochondrion , secretion , cytochalasin b , endoplasmic reticulum , chemistry , biochemistry , phosphorylation , cytoskeleton , cell
Mitochondria play an important role in the homeostasis of intracellular Ca 2+ and regulate its availability for exocytosis. Inhibitors of mitochondria Ca 2+ uptake such as protonophore CCCP potentiate the secretory response to a depolarizing pulse of K + . Exposure of cells to agents that directly (cytochalasin D, latrunculin B) or indirectly (PMA) disrupt cortical F‐actin networks also potentiate the secretory response to high K + . The effects of cytochalasin D and CCCP on secretion were additive whereas those of PMA and CCCP were not; this suggests different mechanisms for cytochalasin D and CCCP and a similar mechanism for PMA and CCCP. Mitochondria were the site of action of CCCP, because the potentiation of secretion by CCCP was observed even after depletion of Ca 2+ from the endoplasmic reticulum. CCCP induced a small increase in the cytosolic Ca 2+ concentration ([Ca 2+ ] c ) that was not modified by the protein kinase C (PKC) inhibitor chelerythrine. Both CCCP and PMA induced cortical F‐actin disassembly, an effect abolished by chelerythrine. In addition, rotenone and oligomycin A, two other mitochondrial inhibitors, also evoked cortical F‐actin disassembly and potentiated secretion; again, these effects were blocked by chelerythrine. CCCP also enhanced the phosphorylation of PKC and myristoylated alanine‐rich C kinase substance (MARCKS), and these were also inhibited by chelerythrine. The results suggest that the rapid sequestration of Ca 2+ by mitochondria would protect the cell from an enhanced PKC activation and cortical F‐actin disassembly, thereby limiting the magnitude of the secretory response.