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Inhibition of cardiac sodium currents in adult rat myocytes by n‐3 polyunsaturated fatty acids
Author(s) -
Leifert Wayne R.,
McMurchie Edward J.,
Saint David A.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.00671.x
Subject(s) - docosahexaenoic acid , eicosapentaenoic acid , polyunsaturated fatty acid , chemistry , linoleic acid , sodium , oleic acid , arachidonic acid , fatty acid , sodium channel , docosapentaenoic acid , biophysics , biochemistry , biology , enzyme , organic chemistry
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 α‐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 EC 50 values of 6.0 ± 1.2, 16.2 ± 1.3 and 26.6 ± 1.3 μM, respectively. 3 Docosahexaenoic acid, eicosapentaenoic acid and α‐linolenic acid at 25 μM 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, α‐linolenic acid and benzyl alcohol significantly increased sarcolemmal membrane fluidity as measured by fluorescence anisotropy (steady‐state, r ss , 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 r ss was not significantly different from control). 6 The potency of the n‐3 fatty acids docosahexaenoic acid, eicosapentaenoic acid and α‐linolenic acid to block cardiac sodium currents is correlated with their ability to produce an increase in membrane fluidity.