Inhibition of ruthenium red-induced Ca2+ efflux from liver mitochondria by the antibiotic X-537A.
It has been reported (Becker, G.L., Fiskum, G. and Lehninger, A.L. (1980) J. Biol. Chem. 255, 9009-9012) that respiring rat liver mitochondria suspended in KC1 medium containing ATP, Mg2+ and phosphate, maintain a steady state extramitochondrial free Ca2+ concentration of about 0.5 microM. The results reported here show that the addition of the antibiotic X-537A, at concentrations far below those required for ionophorous activity, caused a perturbation in this steady state, lowering the extramitochondrial free Ca2+ concentration by about 0.20 microM. This shift in steady state was clarified by a study of X-537A inhibition of the Ca2+ efflux induced by ruthenium red; a half-maximum effect was observed at approximately 25 nM X-537A. No effect on Ca2+ transport through the influx uniporter was observed. The possibility of a generalized stabilizing action of the antibiotic on the mitochondrial membrane seems to be ruled out by its effectiveness at very low concentrations.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D007700:Kinetics; D007832:Lasalocid / Q000494:pharmacology*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012428:Ruthenium / Q000494:pharmacology*; D012430:Ruthenium Red / Q000494:pharmacology*
D012430:Ruthenium Red; D012428:Ruthenium; D002118:Calcium; D007832:Lasalocid