The effects of drugs on calcium uptake and calcium release by mitochondria and sarcoplasmic reticulum of frog skeletal muscle

Abstract

The effects of quinidine, chlorpromazine and caffeine on Ca uptake and Ca release by mitochondria and fragmented sarcoplasmic reticulum (FSR) of frog muscle were studied. Quinidine (1–2 mM) released considerable Ca from preloaded mitochondria but had little effect on preloaded FSR. The uptake of Ca both by mitochondria and FSR was inhibited by higher concentrations (2 or 1 mM) of quinidine but the inhibition of mitochondrial Ca uptake was much greater. With lower concentration (0.4 mM), there was no significant effect on Ca uptake by FSR, but a 48 per cent inhibition of mitochondrial Ca uptake was observed. Chlorpromazine (0.01–0.1 mM) inhibited Ca uptake by both mitochondria and FSR, but the inhibition in the case of FSR was weaker than mitochondria. Only the highest concentration (0.1 mM) of chlorpromazine caused a release of Ca from mitochondria or FSR. Caffeine (2–10 mM) inhibited Ca uptake both by mitochondria and FSR and again the inhibition of Ca uptake by mitochondria was greater than of FSR. Caffeine (10 mM) in contrast to quinidine released Ca from FSR and not from mitochondria. Ca releasing effect of both caffeine and quinidine increased when the ratio of the drug and FSR protein increased. The Ca releasing concentrations of these drugs were comparable to those reported to elicit contractures of living muscle. The lower concentrations which inhibited Ca uptake were comparable to those which potentiate twitch.