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(A) Normalized current-voltage relationship in absence (control) and presence of 5 µM EPA (n=8). (B). Relative whole-cell activation conductance in absence and presence of 5 µM EPA. Normalized activation curves are superimposable, which indicates that EPA has no effect upon activation of Na+ currents. (C) Effects of EPA on normalized steady state inactivation of Na+ current (n=7) in presence and absence of 5 µM EPA and after washout. Shift to the left V1/2 = -23 mV (n=7). This shift of the steady state inactivation potential to more hyperpolarized potentials is an important feature of the action of the n-3 fish oil fatty acids in preventing arrhythmias.
The n-3 fatty acids modulate the ionic currents in the plasma membrane of heart cells and the human myocardial sodium channel expressed in HEK293 cells. There is an effect of the n-3 PUFA on the sodium current, which contributes significantly to their antiarrhythmic action. These fatty acids shift the steady state inactivation to hyperpolarized potentials - see Fig 6. When an ion channel opens, it is considered to be in its activated state. The subsequent closing of the ion channel occurs during its inactivated state. After an action potential, repolarization of the normal myocyte resting potential occurs promptly, but before most sodium channels have recovered to their closed state from which they can respond again with an action potential to another depolarizing stimulus. They are still relatively refractory. But that refractory period can be markedly prolonged by the presence of the n-3 fatty acids, which shift the steady state inactivation to hyperpolarized potentials. This simply means that in the presence of the n-3 PUFA, a considerably longer time or a more negative membrane potential is required to return the sodium channels to their resting, closed but activatable state.