Interaction of charged amphiphiles with Na+-Ca2+ exchange in cardiac sarcolemmal vesicles

Abstract

We have investigated the interaction of several charged amphiphiles with the Na+-Ca2+ exchange mechanism in a highly purified preparation of canine cardiac sarcolemmal vesicles. In all cases, the hydrophobic part of the molecule was an unbranched alkyl group. All anionic lauryl derivatives stimulated (by up to 100%) the initial rate of Na+-Ca2+ exchange in the order lauryl sulfate greater than dodecyl sulfonate greater than lauric acid. All cationic lauryl derivatives (dodecylamine, dodecyltrimethylamine, laurylcholine) were potent inhibitors of Na+-Ca2+ exchange (approximately 50% at 20 microM amphiphile). The effects of the charged amphiphiles on Na+-Ca2+ exchange were not secondary to altered passive ion permeabilities or to altered membrane surface potential. The anionic compound lauryl sulfate stimulated sarcolemmal Na+-Ca2+ exchange activity by increasing the apparent affinity of the exchanger for Ca2+. In contrast, cationic dodecylamine did not change the apparent Km (Ca2+) and acted as a noncompetitive inhibitor of Na+-Ca2+ exchange. The effectiveness of the amphiphiles could be varied by altering the length of the alkyl chain. The more hydrophobic the molecule (i.e. the longer the alkyl chain), the more potent was the stimulation or inhibition of Na+-Ca2+ exchange. This implies that the amphiphiles most probably become embedded in the membrane lipid bilayer to exert effects on Na+-Ca2+ exchange. The Na+-Ca2+ exchange mechanism is more sensitive to the charged amphiphiles than are other sarcolemmal transport mechanisms. We have previously suggested (Philipson, K. D., and Nishimoto, A. Y. (1984) J. Biol. Chem. 259, 16-19) that negatively charged phospholipids could stimulate Na+-Ca2+ exchange activity. We propose that the charged amphiphiles modulate Na+-Ca2+ exchange activity by acting as phospholipid analogues. The amphiphiles are useful tools for studying the interaction of the Na+-Ca2+ exchange mechanism with the lipid bilayer.