Inhibition of cardiac sodium currents in adult rat myocytes by n-3 polyunsaturated fatty acids

Abstract

1. The acute effects of n-3 polyunsaturated fatty acids were determined on whole-cell sodium currents recorded in isolated adult rat ventricular myocytes using patch clamp techniques. 2. The n-3 polyunsaturated fatty acids docosahexaenoic acid (22:6, n-3), eicosapentaenoic acid (20:5, n-3) and alpha-linolenic acid (18:3, n-3) dose-dependently blocked the whole-cell sodium currents evoked by a voltage step to -30 mV from a holding potential of -90 mV with EC50 values of 6.0 +/- 1.2, 16.2 +/- 1.3 and 26.6 +/- 1.3 microM, respectively. 3. Docosahexaenoic acid, eicosapentaenoic acid and alpha-linolenic acid at 25 microM shifted the voltage dependence of activation of the sodium current to more positive potentials by 9.2 +/- 2.0, 10.1 +/- 1.1 and 8.3 +/- 0.9 mV, respectively, and shifted the voltage dependence of inactivation to more negative potentials by 22.3 +/- 0.9, 17.1 +/- 3.7 and 20.5 +/- 1.0 mV, respectively. In addition, the membrane fluidising agent benzyl alcohol (10 mM) shifted the voltage dependence of activation to more positive potentials by 7.8 +/- 2.5 mV and shifted the voltage dependence of inactivation to more negative potentials (by -24.6 +/- 3.6 mV). 4. Linoleic acid (18:2, n-6), oleic acid (18:1, n-9) and stearic acid (18:0) were either ineffective or much less potent at blocking the sodium current or changing the voltage dependence of the sodium current compared with the n-3 fatty acids tested. 5. Docosahexaenoic acid, eicosapentaenoic acid, alpha-linolenic acid and benzyl alcohol significantly increased sarcolemmal membrane fluidity as measured by fluorescence anisotropy (steady-state, rss, values of 0.199 +/- 0. 004, 0.204 +/- 0.006, 0.213 +/- 0.005 and 0.214 +/- 0.009, respectively, compared with 0.239 +/- 0.002 for control), whereas stearic, oleic and linoleic acids did not alter fluidity (the rss was not significantly different from control). 6. The potency of the n-3 fatty acids docosahexaenoic acid, eicosapentaenoic acid and alpha-linolenic acid to block cardiac sodium currents is correlated with their ability to produce an increase in membrane fluidity.