Effects of bepridil on Ca2+ uptake by cardiac mitochondria

Isolated rat heart mitochondria accumulate large amounts of Ca2+ at the expense of respiration-linked energy or of that provided by the hydrolysis of ATP by the mitochondrial ATPase. At concentrations below 10 microM bepridil has no effect on the first mechanism but inhibits the second. At higher concentrations bepridil depresses both. At low concentrations bepridil decreases proton influx into mitochondria in ADP-stimulated respiration while it has no effect on proton ejection in Ca2+-stimulated respiration. A preliminary study shows that bepridil inhibits ATP hydrolysis linked to Ca2+ absorption by mitochondria. The calcium antagonists verapamil, nifedipine and diltiazem exhibit none of these effects.