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Role of ATP decrease in secretion induced by mitochondrial dysfunction in guinea‐pig adrenal chromaffin cells
Author(s) -
Inoue M.,
Fujishiro N.,
Imanaga I.,
Sakamoto Y.
Publication year - 2002
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.2001.012936
Subject(s) - oligomycin , secretion , mitochondrion , depolarization , membrane potential , rhodamine 123 , cytosol , mitochondrial ros , biology , biophysics , inner mitochondrial membrane , reactive oxygen species , chemistry , microbiology and biotechnology , endocrinology , biochemistry , atpase , multiple drug resistance , enzyme , antibiotics
The mechanism related to mitochondrial dysfunction‐induced catecholamine (CA) secretion in dispersed guinea‐pig adrenal chromaffin cells was investigated using amperometry and confocal laser microscopy. Application of CCCP, which does not stimulate generation of reactive oxygen species (ROS), reversibly induced CA secretion, whereas application of either cyanide or oligomycin (OL), a stimulator for ROS, enhanced CA secretion to a smaller extent. The CCCP‐induced secretion was abolished by removal of external Ca 2+ ions and was markedly diminished by D600. The mitochondrial membrane potential, measured using rhodamine 123, was rapidly lost in response to CCCP, but did not change noticeably during a 3 min exposure to OL. Prior exposure to OL markedly facilitated depolarization of the mitochondrial membrane potential in response to cyanide. The mitochondrial inhibitors rapidly produced an increase in Magnesium Green (MgG) fluorescence in the absence of external Ca 2+ and Mg 2+ ions, an increase that was larger in the cytoplasm than in the nucleus. The rank order of potency in increasing MgG fluorescence among the inhibitors was similar to that in increasing secretion. Thus, mitochondrial inhibition rapidly decreases [ATP] and the mitochondrial dysfunction‐induced secretion is not due to ROS generation or to mitochondrial depolarization, but is possibly mediated by a decrease in ATP.