Evidence for the existence of regulatory sites for Ca2+ on the Na+/Ca2+ carrier of cardiac mitochondria.
The Na+-induced efflux of Ca2+ catalysed by the Na+/Ca2+ carrier of cardiac mitochondria is strongly inhibited by extramitochondrial Ca2+. The nature of this inhibition was investigated as follows. (a) The apparent association of external Na+ and the Ca2+ analogue Sr2+ with substrate-binding sites (i.e. those sites involved in cation translocation) is promoted markedly by K+. The inhibition of Na+/Ca2+ exchange by external Ca2+ is affected little by K+. (b) There is a competitive relationship between the binding of external Na+ and external Ca2+ to substrate-binding sites, whereas at low concentrations (less than 4 microM) extramitochondrial Ca2+ is a partial non-competitive inhibitor with respect to external Na+. (c) This inhibiton by external Ca2+ is characterized by a maximal decrease of about 70% in the Vmax of Na+/Ca2+ exchange and by cooperative binding of external Ca2+ to sites that are half saturated by 0.7-0.8 microM free Ca2+. The binding of Ca2+ and Sr2+ to substrate-binding sites shows no co-operativity. These criteria suggest that the Na+/Ca2+ carrier may contain regulatory sites that render the carrier sensitive to changes in extramitochondrial [Ca2+] within the physiological range.
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger; D013324:Strontium / Q000494:pharmacology
D002352:Carrier Proteins; D008565:Membrane Proteins; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D011188:Potassium; D002118:Calcium; D013324:Strontium