期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：5
页码：2680-2685
DOI：10.1073/pnas.95.5.2680
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Studies have shown that fish oils, containing n-3 fatty acids, have protective effects against ischemia-induced, fatal cardiac arrhythmias in animals and perhaps in humans. In this study we used the whole-cell voltage-clamp technique to assess the effects of dietary, free long-chain fatty acids on the Na+ current (INa,) in human embryonic kidney (HEK293t) cells transfected with the -subunit of the human cardiac Na+ channel (hH1). Extracellular application of 0.01 to 30 {micro}M eicosapentaenoic acid (EPA, C20:5n-3) significantly reduced INa, with an IC50 of 0.51 {+/-} 0.06 {micro}M. The EPA-induced suppression of INa, was concentration- and voltage-dependent. EPA at 5 {micro}M significantly shifted the steady-state inactivation relationship by -27.8 {+/-} 1.2 mV (n = 6, P < 0.0001) at the V1/2 point. In addition, EPA blocked INa, with a higher "binding affinity" to hH1 channels in the inactivated state than in the resting state. The transition from the resting state to the inactivated state was markedly accelerated in the presence of 5 {micro}M EPA. The time for 50% recovery from the inactivation state was significantly slower in the presence of 5 {micro}M EPA, from 2.1 {+/-} 0.8 ms for control to 34.8 {+/-} 2.1 ms (n = 5, P < 0.001). The effects of EPA on INa, were reversible. Furthermore, docosahexaenoic acid (C22:6n-3), -linolenic acid (C18:3n-3), conjugated linoleic acid (C18:2n-7), and oleic acid (C18:1n-9) at 5 {micro}M and all-trans-retinoic acid at 10 {micro}M had similar effects on INa, as EPA. Even 5 {micro}M of stearic acid (C18:0) or palmitic acid (C16:0) also significantly inhibited INa,. In contrast, 5 {micro}M EPA ethyl ester did not alter INa, (8 {+/-} 4%, n = 8, P > 0.05). The present data demonstrate that free fatty acids suppress INa, with high "binding affinity" to hH1 channels in the inactivated state and prolong the duration of recovery from inactivation.
