Inhibition of Na+‐dependent Ca2+ efflux from heart mitochondria by amiloride analogues

Abstract

The Na⁺-induced release of accumulated Ca²⁺ from heart mitochondria is inhibited by amiloride, benzamil and several other amiloride analogues. These drugs do not affect uptake or release of Ca²⁺ mediated by the ruthenium red-sensitive uniporter and their effects, like those of diltiazem and other Ca²⁺-antagonists, appear to be localized principally at the Na⁺/Ca²⁺ antiporter of the mitochondrion. Benzamil inhibits Na⁺/Ca²⁺ antiport non-competitively with respect to [Na⁺] with a K _i of 167 μM. In the presence of 1.5 mM P_i the K _i for benzamil inhibition of this reaction is decreased to 87 μM.