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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.
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