Ca2+ release from energetically coupled tumor mitochondria.
A Na+/Ca2+ exchange activity for Ca2+ efflux has been identified in isolated Ehrlich ascites tumor mitochondria. Further, under conditions favoring cycling of Ca2+ across the mitochondrial inner membrane, extramitochondrial [Ca2+] also was shown to be Na+-dependent. The Na+/Ca2+ exchange showed sigmoidal kinetics with a mean (+/-SD) [Na+] required for half maximal stimulation of Ca2+ efflux of 8.4 +/- 3.8 mM and a Hill coefficient of 1.6. Na+/Ca2+ exchange was very sensitive to inhibition by the Ca2+ antagonist diltiazem (56% inhibition at 7.5 nmoles X mg protein-1) whereas a number of other compounds, including verapamil, nupercaine, and trifluoperazine were less effective in inhibiting Ca2+ efflux. These data demonstrate for the first time the presence of a pathway in tumor mitochondria for unidirectional Ca2+ efflux induced by Na+, and provide a mechanism for regulation of tumor intra- and extramitochondrial [Ca2+]. Results of the present study support the need for further study of intracellular Na+ and its role in regulation of Ca2+ homeostasis in tumor cells.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002460:Cell Line; D003992:Dibucaine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D014268:Trifluoperazine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D012964:Sodium; D014700:Verapamil; D003992:Dibucaine; D002118:Calcium