Inhibition of Na+-Ca2+ exchange in rat brain by amiloride.

Amiloride (N-amidino-3,5-diamino-6-chloropyrazine carboxamide) reversibly inhibits Na+-dependent 45Ca2+ uptake (Na+-Ca2+ exchange) by plasmalemma-enriched vesicles prepared from microsomes of rat cerebral cortex and by vesicles from osmotically shocked synaptosomes. The drug inhibits Na+-dependent Ca2+ uptake in a competitive manner with a KI of 0.25-0.34 mM. Na+-dependent 45Ca2+ efflux from vesicles is also inhibited by extravesicular amiloride. The drug does not appear to affect nonmitochondrial ATP-dependent Ca2+ transport in these vesicle preparations. Membranes containing Na+-Ca2+ carrier can be solubilized in Na+-cholate and reconstituted into phospholipid vesicles. Na+-dependent Ca2+ uptake by the vesicles is inhibited by amiloride.