Abstract
Background Accumulating evidence has suggested that ω-3-polyunsaturated fatty acids (ω-3-PUFAs) may have beneficial effects in the prevention/treatment of cardiovascular diseases, but controversies remain regarding their antiarrhythmic potentials. Whether ω-3 PUFAs can suppress early afterdepolarizations (EADs) induced by oxidative stress remains unclear. Methods and Results We recorded action potentials (APs) using the current-clamp mode of the patch-clamp technique in ventricular myocytes isolated from rabbit hearts. Treatment of myocytes with H 2 O 2 (200 μM) prolonged action potential durations (APDs) and induced EADs, which were significantly suppressed by docosahexaenoic acid (DHA, 10 or 25 μM, n = 8). To reveal the ionic mechanisms, we used the voltage-clamp mode and examined the effects of DHA on L-type calcium currents (I Ca,L ), late sodium current (I Na ), and transient outward potassium currents (I to ) in ventricular myocytes pretreated with H 2 O 2 . H 2 O 2 (200 μM) increased I Ca,L by 46.4% from control (–8.4 ± 1.4 pA/pF) to a peak level (–12.3 ± 1.8 pA/pF, n = 6, P 2 O 2 perfusion. H 2 O 2 -enhanced I Ca,L was significantly reduced by DHA (25 μM) (–7.1 ± 0.9 pA/pF at steady state, n = 6, P Na increased by H 2 O 2 (from –0.7 ± 0.1 pC to –3.2 ± 0.3 pC) was completely reversed (to –0.8 ± 0.2 pC, n = 5) by DHA (25 μM). H 2 O 2 also increased the peak amplitude and the steady state of I to from 8.9 ± 1.0 and 2.16 ± 0.25 pA/pF to 12.8 ± 1.21 and 3.13 ± 0.47 pA/pF, respectively (n = 6, P to altered by H 2 O 2 . In addition, DHA (25 μM) did not affect the increase of intracellular reactive oxygen species (ROS) levels induced by H 2 O 2 in rabbit ventricular myocytes. Conclusions These findings demonstrate that DHA suppresses exogenous H 2 O 2 -induced EADs, mainly by modulating membrane ion channel functions, while its direct effect on ROS plays a less prominent role.
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