THE ROLE OF THE NA+/H+ EXCHANGE SYSTEM IN CARDIAC-CELLS IN RELATION TO THE CONTROL OF THE INTERNAL NA+ CONCENTRATION - A MOLECULAR-BASIS FOR THE ANTAGONISTIC EFFECT OF OUABAIN AND AMILORIDE ON THE HEART

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 259  (14) , 8880-8885
Abstract
Cardiac cells in culture (from rat and chick heart) have a membrane Na+/H+ exchange system that is inhibited by amiloride (K0.5 = 5 .mu.M) and by its more potent N-5-disubstituted derivatives dimethylamiloride (K0.5 = 300 nM). The properties of the cardiac Na+/H+ exchange system are similar to those found for the Na+/H+ exchanger in other cellular types. The Na+/H+ exchange system is a major pathway for Na+ uptake by cardiac cells. Ouabain which inhibits the (Na+,K+)-ATPase, a major pathway for Na+ efflux, is known to provoke Na+ accumulation and to stimulate 45Ca2+ entry via the Na+/Ca2+ exchange mechanism, thereby producing an inotropic effect. N-5-disubstituted amiloride derivatives, by blocking Na+ entry into cardiac cells, antagonize both ouabain-induced intracellular Na+ accumulation and the ouabain-induced acceleration of 45Ca2+ uptake.

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