Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress.

TitleInhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress.
Publication TypeJournal Article
Year of Publication1988
AuthorsCrompton, M, Ellinger, H, Costi, A
JournalBiochem J
Volume255
Issue1
Pagination357-60
Date Published1988 Oct 01
ISSN0264-6021
KeywordsAnimals, Calcium, Cell Membrane Permeability, Cyclosporins, Female, Intracellular Membranes, Membrane Potentials, Mitochondria, Heart, Oxidation-Reduction, Peroxides, Phosphates, Rats, Rats, Inbred Strains, Sucrose, tert-Butylhydroperoxide
Abstract

The capacity of cyclosporin A to inhibit opening of a Ca2+-dependent pore in the inner membrane of heart mitochondria was investigated. Whereas in the presence of 25 nmol of Ca2+/mg of mitochondrial protein and 5 mM-Pi mitochondria were unable to maintain accumulated Ca2+, inner-membrane potential and sucrose impermeability, all three parameters were preserved when cyclosporin was included. Pore opening was assayed directly by [14C]sucrose entry and entrapment in the matrix space. [14C]Sucrose entry induced by both Ca2+ plus Pi and Ca2+ plus t-butyl hydroperoxide was almost completely inhibited by 60 pmol of cyclosporin/mg of mitochondrial protein. It is concluded that cyclosporin A is a potent inhibitor of the pore.

Alternate JournalBiochem. J.
Citation KeyPMID3196322
PubMed ID3196322
PubMed Central IDPMC1135230