Docosahexaenoic Acid reduces the incidence of early afterdepolarizations caused by oxidative stress in rabbit ventricular myocytes.

ABSTRACT

Accumulating evidence has suggested that ω3-polyunsaturated fatty acids (ω3-PUFAs) may have beneficial effects in the prevention/treatment of cardiovascular diseases, while controversies still remain regarding their anti-arrhythmic potential. It is not clear yet whether ω-3-PUFAs can suppress early afterdepolarizations (EADs) induced by oxidative stress. In the present study, we recorded action potentials using the patch-clamp technique in ventricular myocytes isolated from rabbit hearts. The treatment of myocytes with H(2)O(2) (200 µM) prolonged AP durations and induced EADs, which were significantly suppressed by docosahexaenoic acid (DHA, 10 or 25 µM; n = 8). To reveal the ionic mechanisms, we examined the effects of DHA on L-type calcium currents (I(Ca.L)), late sodium (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 < 0.01) after 6 min of H(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, n = 6, p < 0.01). Similarly, H(2)O(2)-increased the late I(Na) (-3.2 ± 0.3 pC) from control level (-0.7 ± 0.1 pC). DHA (25 µM) completely reversed the H(2)O(2)-induced increase in late I(Na) (to -0.8 ± 0.2 pC, n = 5). H(2)O(2) also increased the peak amplitude of and the steady state 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 < 0.01, however, treatment with DHA (25 µM) did not produce significant effects on current amplitudes and dynamics of I(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. 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 may play a less prominent role.