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.
Highlights
We haveinvestigated the interaction of several traction, and Na+-Ca2+exchange has been implicated as a charged amphiphiles with the Na+-Ca”+ exchange regulator of this critical Ca2+flux [2,3]
Tions of the negatively charged amphiphile lauryl sulfate At this concentration, inhibition is due to a direct effect on stimulates the initial rateof Na+-Ca2+exchange activity
A series of such experiments (Table 11) shows that the effect of lauryl sulfate is primarily if the primary effect of the lauryl sulfate were to increase to increase the apparent affinity of the exchange mechanism vesicle Ca2+permeability, Na+-Ca2+exchange would appear for Ca2+.In contrast, the positively charged amphiphile doto be inhibited
Summary
Parent K, (Ca”’) 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. (i.e. the longer the alkyl chain), themore potent was h and was purified 58.7-fold as compared with the initial tissue the stimulation or inhibition of Na+-Ca”+ exchange. This implies that the amphiphiles most probably become embeddedin themembrane lipid bilayer to exert effects on Na+-Ca”+exchange. The Na’-Ca”’ exchange mechanism is more sensitive to the charged amphiphiles than are other sarcolemmal transport mechanisms. 19) that negatively charged phospholipids could stim- diluted into 0.25 ml of Ca” uptake medium containing 140 mM KCl, ulate Na+-Ca”+exchange activity. We propose that the 10 p~ CaClz,0.3 pCi of‘6CaC12,0.4 PM valinomycin, 10 mM Mops charged amphiphiles modulate Na+-Ca2+exchange activity by acting as phospholipid analogues.
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