Permeability transition pore closure promoted by quinine.

The mitochondrial membrane permeability transition induced by Ca2+ is inhibited by quinine in a dose-dependent fashion. Competition experiments strongly suggest that quinine displaces Ca2+ bound to the inner membrane. This is supported by experiments showing that quinine inhibits Ca2+-dependent but not Ca2+-independent mitochondrial swelling induced by phenylarsine oxide. As with Ca2+ chelators, quinine induces permeability transition pore closure preventing the contraction induced by poly(ethylene glycol) 2000 in mitochondria preswollen by incubation in KSCN medium containing Ca2+ and inorganic phosphate. These results suggest that quinine dislodges Ca2+ bound to the protein site, which triggers pore opening.