Increased Susceptibility of Striatal Mitochondria to Calcium-Induced Permeability Transition

Mitochondria were simultaneously isolated from striatum and cortex of adult rats and compared in functional assays for their sensitivity to calcium activation of the permeability transition. Striatal mitochondria showed an increased dose-dependent sensitivity to Ca2+ compared with cortical mitochond...

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Bibliographic Details
Published in:	The Journal of neuroscience Vol. 23; no. 12; pp. 4858 - 4867
Main Authors:	Brustovetsky, Nickolay, Brustovetsky, Tatiana, Purl, Kevin J, Capano, Michela, Crompton, Martin, Dubinsky, Janet M
Format:	Journal Article
Language:	English
Published:	United States Soc Neuroscience 15-06-2003 Society for Neuroscience
Subjects:	Adenosine Diphosphate - pharmacology Adenosine Triphosphate - chemistry Adenosine Triphosphate - metabolism Animals Calcium - pharmacokinetics Calcium - pharmacology Cellular/Molecular Cerebral Cortex - chemistry Corpus Striatum - chemistry Cyclophilins - analysis Cyclophilins - metabolism Dose-Response Relationship, Drug Electron Transport - drug effects Electron Transport - physiology Enzyme Inhibitors - pharmacology Female Huntington Disease - etiology Huntington Disease - metabolism Light Male Membrane Potentials - drug effects Membrane Potentials - physiology Mitochondria - chemistry Mitochondria - drug effects Mitochondria - metabolism Peptidyl-Prolyl Isomerase F Permeability - drug effects Rats Reactive Oxygen Species - chemistry Scattering, Radiation
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Summary:	Mitochondria were simultaneously isolated from striatum and cortex of adult rats and compared in functional assays for their sensitivity to calcium activation of the permeability transition. Striatal mitochondria showed an increased dose-dependent sensitivity to Ca2+ compared with cortical mitochondria, as measured by mitochondrial depolarization, swelling, Ca2+ uptake, reactive oxygen species production, and respiration. Ratios of ATP to ADP were lower in striatal mitochondria exposed to calcium despite equal amounts of ADP and ATP under respiring and nonrespiring conditions. The Ca2+-induced changes were inhibited by cyclosporin A or ADP. These responses are consistent with Ca2+ activation of both low and high permeability pathways constituting the mitochondrial permeability transition. In addition to the striatal supersensitivity to induction of the permeability transition, cyclosporin A inhibition was less potent in striatal mitochondria. Immunoblots indicated that striatal mitochondria contained more cyclophilin D than cortical mitochondria. Thus striatal mitochondria may be selectively vulnerable to the permeability transition. Subsequent mitochondrial dysfunction could contribute to the initial toxicity of striatal neurons in Huntington's disease.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0270-6474 1529-2401
DOI:	10.1523/jneurosci.23-12-04858.2003