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Differences in the Activation of the Mitochondrial Permeability Transition Among Brain Regions in the Rat Correlate with Selective Vulnerability
Author(s) -
Friberg Hans,
Connern Cathal,
Halestrap Andrew P.,
Wieloch Tadeusz
Publication year - 1999
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.1471-4159.1999.0722488.x
Subject(s) - mitochondrion , mitochondrial permeability transition pore , cerebellum , swelling , chemistry , hippocampus , biochemistry , biology , biophysics , microbiology and biotechnology , endocrinology , programmed cell death , apoptosis , pathology , medicine
Mitochondria from different regions of the brain wereprepared, and the activation of the mitochondrial permeability transition(MPT) by calcium was investigated by monitoring the associated mitochondrialswelling. In general, the properties of the MPT in brain mitochondria werefound to be qualitatively similar to those observed in liver and heartmitochondria. Thus, swelling was inhibited by adenine nucleotides (AdNs) andlow pH (<7.0), whereas thiol reagents and alkalosis facilitated swelling.Cyclosporin A and its nonimmunosuppressive analogue N ‐methyl‐Val‐4‐cyclosporin A (PKF 220‐384) both inhibited swellingand prevented the translocation of cyclophilin D from the matrix to themembranes of cortical mitochondria. However, the calcium sensitivity of theMPT differed in mitochondria from three brain regions (hippocampus > cortex> cerebellum) and is correlated with the susceptibility of these regions toischemic damage. Depleting mitochondria of AdNs by treatment withpyrophosphate ions sensitized the MPT to [Ca 2+ ] and abolished regional differences, implying regional differences in mitochondrial AdN content. This was confirmed by measurements showing significant differences in AdN content among regions (cerebellum > cortex > hippocampus). Our data add to recent evidence that the MPT may be involved in neuronal death.