Inhibition of brain mitochondrial Ca2+ transport by amiloride analogues

Rat brain mitochondrial Ca2+ uptake and release were examined in the presence of amiloride (3,5-diamino-6-chloro-N-(diaminomethylene)-pyrazinecarboxamide) and nineteen amiloride analogues. Amiloride, an inhibitor of Na+-Ca2+ exchange in plasmalemma membranes, did not affect energy-dependent Ca2+ uptake, whereas several other analogues were inhibitors. Similarly, amiloride did not alter Ca2+ release in the presence or absence of Na+. However, some analogues were found that stimulated and others that inhibited Ca2+ release. While many of these analogues reduced mitochondrial respiratory control ratios, two analogues were identified which inhibited Ca2+ uptake but did not alter mitochondrial respiratory control. Similarly two analogues were identified which inhibited Ca2+ efflux without affecting respiratory control.