Effects of fatty acids on Na/Ca exchange in cardiac sarcolemmal membranes

Three structurally distinct amphiphiles palmitic acid, oleic acid, and palmityl carnitine were studied to determine their effects on sodium dependent calcium uptake by purified cardiac sarcolemmal vesicles (PSL). Sodium dependent calcium uptake by PSL when studied over a 20 min reaction period was composed of an initial rapid uptake (20.9 +/- 0.93 nmol/mg X 30 s, mean +/- S.E. n = 20) a plateau in calcium content (42.4 +/- 3.2 nmol/mg, mean +/- S.E. n = 20) and a slow spontaneous release characterized by a first order rate constant of 0.68 +/- 0.08/h (mean +/- S.E. n = 18). Both palmityl carnitine and palmitic acid inhibited, whereas oleic acid stimulated initial calcium uptake. All three amphiphiles shortened the time to peak calcium content, inhibited peak calcium content and increased the rate constant for calcium release. All these effects were observed at fatty acid: membrane phospholipid mole ratios of 0.67 : 1 to 1.67 : 1 for oleic acid and palmityl carnitine and 0.02 : 1 to 0.42 : 1 for palmitic acid. These effects do not reflect disruption of membrane vesicle structure and may be explained, at least in part, by amphiphile induced increases in sarcolemmal membrane ion permeability. Although amphiphile accumulation has been implicated in the pathogenesis of cellular abnormalities in the ischemic myocardium, this study has shown that large amounts of amphiphile relative to membrane lipid are required to alter sarcolemmal membrane function in vitro.