Effects of n-3 Polyunsaturated Fatty Acids on Cardiac Ion Channels

Abstract

Dietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, and these effects have been attributed to their capability to modulate ion channels. In the present review, we will focus on the effects of PUFAs on a cardiac sodium channel (Na(v)1.5) and two potassium channels involved in cardiac atrial and ventricular repolarization (K(v)) (K(v)1.5 and K(v)11.1). n-3 PUFAs of marine (docosahexaenoic, DHA and eicosapentaenoic acid, EPA) and plant origin (alpha-linolenic acid, ALA) block K(v)1.5 and K(v)11.1 channels at physiological concentrations. Moreover, DHA and EPA decrease the expression levels of K(v)1.5, whereas ALA does not. DHA and EPA also decrease the magnitude of the currents elicited by the activation of Na(v)1.5 and calcium channels. These effects on sodium and calcium channels should theoretically shorten the cardiac action potential duration (APD), whereas the blocking actions of n-3 PUFAs on K(v) channels would be expected to produce a lengthening of cardiac action potential. Indeed, the effects of n-3 PUFAs on the cardiac APD and, therefore, on cardiac arrhythmias vary depending on the method of application, the animal model, and the underlying cardiac pathology.

Keywords: arrhythmias; atrial fibrillation; heart failure; n−3 PUFAs.

Figure 1

Structure of the main n− 3 (EPA, DHA, and ALA), n− 6 (AA and LA), monounsaturated (OA), and saturated (SA and PA) PUFAs present in the human diet. Taken from the free ChemSpider Database (http://www.chemspider.com/).

Figure 2

Cardiac AP, ionic currents involved in its genesis and maintenance, and the effects of n− 3 PUFAs on each current under acute and chronic conditions. ↑, Increase; ↓, decrease; or ∼, no changes in the current amplitude. *Studied in human atria. ?, Not tested. With permission from Ravens and Cerbai (2008).