AUTHOR=Zhao Zhenghang , Wen Hairuo , Fefelova Nadezhda , Allen Charelle , Guillaume Nancy , Xiao Dandan , Huang Chen , Zang Wei-Jin , Gwathmey Judith K., Xie Lai-Hua 

TITLE=Docosahexaenoic Acid Reduces the Incidence of Early Afterdepolarizations Caused by Oxidative Stress in Rabbit Ventricular Myocytes

JOURNAL=Frontiers in Physiology

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2012.00252

DOI=10.3389/fphys.2012.00252

ISSN=1664-042X

ABSTRACT=<p>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<sub>2</sub>O<sub>2</sub> (200 μM) prolonged AP durations and induced EADs, which were significantly suppressed by docosahexaenoic acid (DHA, 10 or 25 μM; <italic>n</italic> = 8). To reveal the ionic mechanisms, we examined the effects of DHA on L-type calcium currents (<italic>I</italic><sub>Ca.L</sub>), late sodium (<italic>I</italic><sub>Na</sub>), and transient outward potassium currents (<italic>I</italic><sub>to</sub>) in ventricular myocytes pretreated with H<sub>2</sub>O<sub>2</sub>. H<sub>2</sub>O<sub>2</sub> (200 μM) increased <italic>I</italic><sub>Ca.L</sub> by 46.4% from control (−8.4 ± 1.4 pA/pF) to a peak level (−12.3 ± 1.8 pA/pF, <italic>n</italic> = 6, <italic>p</italic> &lt; 0.01) after 6 min of H<sub>2</sub>O<sub>2</sub> perfusion. H<sub>2</sub>O<sub>2</sub>-enhanced <italic>I</italic><sub>Ca.L</sub> was significantly reduced by DHA (25 μM; −7.1 ± 0.9 pA/pF, <italic>n</italic> = 6, <italic>p</italic> &lt; 0.01). Similarly, H<sub>2</sub>O<sub>2</sub>-increased the late <italic>I</italic><sub>Na</sub> (−3.2 ± 0.3 pC) from control level (−0.7 ± 0.1 pC). DHA (25 μM) completely reversed the H<sub>2</sub>O<sub>2</sub>-induced increase in late <italic>I</italic><sub>Na</sub> (to −0.8 ± 0.2 pC, <italic>n</italic> = 5). H<sub>2</sub>O<sub>2</sub> also increased the peak amplitude of and the steady state <italic>I</italic><sub>to</sub> 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 (<italic>n</italic> = 6, <italic>p</italic> &lt; 0.01, however, treatment with DHA (25 μM) did not produce significant effects on current amplitudes and dynamics of <italic>I</italic><sub>to</sub> altered by H<sub>2</sub>O<sub>2</sub>. In addition, DHA (25 μM) did not affect the increase of intracellular reactive oxygen species (ROS) levels induced by H<sub>2</sub>O<sub>2</sub> in rabbit ventricular myocytes. These findings demonstrate that DHA suppresses exogenous H<sub>2</sub>O<sub>2</sub>-induced EADs mainly by modulating membrane ion channel functions, while its direct effect on ROS may play a less prominent role.</p>