This is a review of our present understanding of the mechanism by which the n-3 polyunsaturated fatty acids (PUFA) in fish oils prevent fatal ventricular arrhythmias in animals and cultured heart cells.

A brief review of three clinical trials that suggest that these PUFAs prevent sudden cardiac death is also included in order to emphasize the potential importance of these fatty acids in human nutrition.

The PUFAs act by stabilizing electrically every cardiac myocyte by modulating conductance of ion channels in the sarcolemma, particularly the fast, voltage-dependent sodium current and the L-type calcium currents, though other ion currents are also affected. Work in progress suggests that the primary site of action of the PUFAs may be on the phospholipid bilayer of the heart cells in the microdomains through which the ion channels penetrate the membrane bilayer in juxtaposition with the ion channels rather than directly on the channel protein itself.

These PUFAs then allosterically alter the conformation and conductance of the channels. Both potential benefits and possible adverse effects of the PUFAs in man will be discussed.

Knowing that the ion channels have been structurally conserved among all excitable tissues, we tested their effects on the electrophysiology of rat hippocampal CA1 neurons and found that the sodium and calcium ion channels in these neurons were also affected by PUFAs.

An attempt to show the place of the PUFAs in human nutrition during the 2-4 million years of our evolution will conclude the review.