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

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 Pi the K i for benzamil inhibition of this reaction is decreased to 87 μM.