calcimycin and potassium-thiocyanate

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.

Topics: Animals; Antimycin A; Calcimycin; Calcium; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; Intracellular Membranes; Kinetics; Membrane Potentials; Mitochondria; Mitochondria, Liver; Mitochondrial Swelling; Onium Compounds; Organophosphorus Compounds; Permeability; Quinine; Rats; Thiocyanates

Addition of A23187 plus EDTA to energized mitochondria in KCl medium determines a rapid osmotic swelling due to K+ uptake. The swelling is fully reversed by uncoupler, is stimulated by quinine, and is accompanied by membrane depolarization and increased rate of respiration. A23187-treated mitochondria passively swell in K+ thiocyanate at neutral pH, under conditions where the H+-K+ antiporter appears to be silent. These data indicate that A23187 activates electrophoretic K+ flux, supporting the notion that Mg2+ depletion unmasks several ionic conductance pathways whose concerted interplay could provide a sensitive regulation of mitochondrial volume homeostasis.

Topics: Calcimycin; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; Intracellular Membranes; Kinetics; Membrane Potentials; Mitochondria; Mitochondrial Swelling; Potassium; Potassium Chloride; Quinine; Thiocyanates; Valinomycin