Docosahexaenoic Acid reduces the incidence of early afterdepolarizations caused by oxidative stress in rabbit ventricular myocytes.
Docosahexaenoic Acid reduces the incidence of early afterdepolarizations caused by oxidative stress in rabbit ventricular myocytes.
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二十二碳六烯酸降低兔心室肌细胞氧化应激引起的早期后除极的发生率
DOI：
10.3389/fphys.2012.00252
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发表时间：
2012
影响因子：
4
通讯作者：
Xie LH
中科院分区：
文献类型：
--
作者：
Zhao Z;Wen H;Fefelova N;Allen C;Guillaume N;Xiao D;Huang C;Zang W;Gwathmey JK;Xie LH
ω3-多不饱和脂肪酸（ω3-PUFAs）在心血管疾病的预防和治疗中具有重要作用，但其抗心血管疾病的作用仍存在争议。ω-3-PUFAs是否能抑制氧化应激诱导的早期后去极化（埃兹）尚不清楚。在本研究中，我们记录动作电位的膜片钳技术在心室肌细胞分离从兔心脏。用H2 O2（200 μM）处理心肌细胞可延长AP持续时间并诱导埃兹，而二十二碳六烯酸（DHA，10或25 μM; n = 8）可显著抑制EAD。为了揭示离子机制，我们研究了DHA对H2 O2预处理的心室肌细胞L-型钙电流（伊卡.L）、晚期钠电流（INa）和瞬时外向钾电流（Ito）的影响。H2 O2（200 μM）使伊卡.L从对照（−8.4 ± 1.4 pA/pF）增加46.4%，在H2 O2灌注6分钟后达到峰值水平（−12.3 ± 1.8 pA/pF，n = 6，p < 0.01）。DHA显著降低了H2 O2增强的伊卡.L（25 μM; −7.1 ± 0.9 pA/pF，n = 6，p < 0.01）。同样，H2 O2-使晚期INa（−3.2 ± 0.3 pC）从对照水平（−0.7 ± 0.1 pC）增加。DHA（25 μM）完全逆转了H2 O2诱导的晚期INa增加（至−0.8 ± 0.2 pC，n = 5）。H2 O2还使Ito的峰值幅度和稳态Ito分别从8.9 ± 1.0和2.16 ± 0.25 pA/pF增加到12.8 ± 1.21和3.13 ± 0.47 pA/pF（n = 6，p < 0.01，然而，用DHA（25 μM）处理对H2 O2改变的Ito的电流幅度和动力学没有产生显著影响。此外，DHA（25 μM）不影响H2 O2诱导的兔心室肌细胞内活性氧（ROS）水平的增加。这些结果表明，DHA抑制外源性H2 O2诱导的埃兹主要是通过调节膜离子通道功能，而其对ROS的直接作用可能发挥不太突出的作用。
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 H2O2 (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 (ICa.L), late sodium (INa), and transient outward potassium currents (Ito) in ventricular myocytes pretreated with H2O2. H2O2 (200 μM) increased ICa.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 H2O2 perfusion. H2O2-enhanced ICa.L was significantly reduced by DHA (25 μM; −7.1 ± 0.9 pA/pF, n = 6, p < 0.01). Similarly, H2O2-increased the late INa (−3.2 ± 0.3 pC) from control level (−0.7 ± 0.1 pC). DHA (25 μM) completely reversed the H2O2-induced increase in late INa (to −0.8 ± 0.2 pC, n = 5). H2O2 also increased the peak amplitude of and the steady state Ito 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 Ito altered by H2O2. In addition, DHA (25 μM) did not affect the increase of intracellular reactive oxygen species (ROS) levels induced by H2O2 in rabbit ventricular myocytes. These findings demonstrate that DHA suppresses exogenous H2O2-induced EADs mainly by modulating membrane ion channel functions, while its direct effect on ROS may play a less prominent role.
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影响因子：
5
作者：
Zhao Z;Fefelova N;Shanmugam M;Bishara P;Babu GJ;Xie LH
通讯作者：
Xie LH
DOI：
10.1097/mco.0b013e3282f44bdf
发表时间：
2008-03-01
影响因子：
3.1
作者：
von Schacky, Clemens
通讯作者：
von Schacky, Clemens
影响因子：
5.5
作者：
Ward, CA;Giles, WR
通讯作者：
Giles, WR
影响因子：
3.3
作者：
Mas, Emilie;Woodman, Richard J.;Mori, Trevor A.
通讯作者：
Mori, Trevor A.
影响因子：
7.4
作者：
Jahangiri, A;Leifert, WR;McMurchie, EJ
通讯作者：
McMurchie, EJ