This figure shows the effect of EPA on the resting myocyte held at a potential of –150 mV (Fig. 7A) and an inactivated partially depolarized myocytes held at a potential of –70 mV (Fig. 7B) in hH1α (human myocardial Na+ channels transiently expressing both the α- and β1-subunits in HEK293 cells). It can be seen that from a membrane potential held at –150 mV, even in the presence of 5 µM EPA, the inward Na+ current is decreased but is still a sufficiently robust INa to induce an action potential, which would propagate through the heart and cause a normal cardiac contraction. By contrast, in the partially depolarized cell with a membrane potential held at –70 mV even the control current was much reduced. This current, however, would likely induce an aberrant action potential and with the nonhomogeneous conduction rates of action potentials in the ischemic myocardium cause a fatal, reentrant arrhythmia. But in the presence of the same 5 µM concentration of EPA any INa would be eliminated. This is what we mean in saying that partially depolarized myocytes would be eliminated from any proarrhythmic effects in the presence of n-3 PUFAs.
This effect of the n-3 PUFAs on Na+ channels, together with their effect to inhibit L-type Ca2+ channels preventing triggered arrhythmic after-potential discharges due to excessive cytosolic Ca2+ fluctuations, we currently think are the major mechanisms for the antiarrhythmic effects of these PUFAs.