Effect of calcium channel antagonists on calcium uptake and release by isolated rat cardiac mitochondria.
The effects of calcium channel antagonists on Ca2+ uptake and Na+-induced Ca2+ release were studied in isolated rat cardiac mitochondria. Diltiazem, nitrendipine and nimodipine were more effective inhibitors of Na+-induced Ca2+ release (IC50 = 19-100 microM) than of Ca2+ uptake (IC50 = 0.2-1 mM). Nitrendipine and nimodipine had virtually identical IC50 values for inhibiting Ca2+ uptake, but nitrendipine was 3-4 times more potent than nimodipine at inhibiting Na+-induced Ca2+ release. If these calcium channel antagonists achieve intracellular concentrations in the range of 10(-5)-10(-4) M, our results suggest that calcium channel antagonists would preferentially inhibit mitochondrial calcium release more than mitochondrial calcium uptake.
Buss
W C
WC
Department of Pharmacology, University of New Mexico, School of Medicine, Albuquerque 87131.
Savage
D D
DD
Stepanek
J
J
Little
S A
SA
McGuffee
L J
LJ
D000818:Animals; D001386:Azides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012430:Ruthenium Red; D012964:Sodium / Q000494:pharmacology
D001386:Azides; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D012430:Ruthenium Red; D012964:Sodium; D002118:Calcium