Amiloride and diltiazem inhibition of microsomal and mitochondrial Na+ and Ca2+ transport.

Amiloride, a K+-sparing diuretic, and diltiazem, a Ca2+ channel antagonist, have both been reported to inhibit Na+ transport-associated processes in different subcellular membrane systems. In this report, similar inhibitory effects of both agents are demonstrated on Na+-induced Ca2+ release from rabbit heart mitochondria and on Na+ uptake in a kidney medulla microsomal preparation. Both amiloride and diltiazem produce 50% inhibition of Na+ uptake in kidney microsomes at the same concentrations. Heart mitochondrial Na+-induced Ca2+ release was 50% inhibited by 6 microM diltiazem and 200 microM amiloride. No effects of either agent on mitochondrial respiratory activity were observed. The results suggest a specific effect of both drugs on a Na+-binding site associated with an antiport exchange process. These data also extend previous observations suggesting the use of these agents as tools to define further ion transport mechanisms in biological membranes.