Wang Ru-xing, Li Ku-lin, Zhang Chang-ying, Zheng Jie, Guo Su-xia, Wu Ying, Li Xiao-rong, Chai Qiang, Lu Tong, Lee Hon-chi
Department of Cardiology, Wuxi People's Hospital Affiliated to Nangjing Medical University, Wuxi 214023, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2011 Apr;39(4):348-52. doi: 10.3760/cma.j.issn.0253-3758.2011.04.014.
To investigate the mechanism of enhanced large conductance calcium-activated potassium channel currents (BK) in coronary smooth muscle cells (SMCs) by docosahexaenoic acid (DHA).
Coronary SMCs were isolated by enzyme digestion. Potassium channels in coronary SMCs were identified by applications of different potassium blockers. Effects of DHA and its metabolite 16, 17-epoxydocosapentaenoic acid (16, 17-EDP) on BK channels in the absence and presence of cytochrome P450 epoxygenase inhibitor SKF525A were studied by patch clamp in whole-cell configuration.
BK channels were widely distributed in SMCs, and BK currents in normal SMCs accounted for (64.2 ± 2.7)% of total potassium currents (n = 20). DHA could activate BK channels, and its 50% effective concentration (EC(50)) was (0.23 ± 0.03) µmol/L, however, the effect of DHA on BK channels was abolished after SMCs were incubated with cytochrome P450 epoxygenase inhibitor SKF525A. 16, 17-EDP, a metabolite of DHA, could reproduce the effects of DHA on BK channels, and its EC(50) was (19.7 ± 2.8) nmol/L.
DHA and metabolites can activate BK channels and dilate coronary arteries through activating cytochrome P450 epoxygenase pathway.
研究二十二碳六烯酸（DHA）增强冠状动脉平滑肌细胞（SMC）中大电导钙激活钾通道电流（BK）的机制。
采用酶消化法分离冠状动脉SMC。应用不同的钾通道阻滞剂鉴定冠状动脉SMC中的钾通道。采用全细胞膜片钳技术研究在有无细胞色素P450环氧化酶抑制剂SKF525A的情况下DHA及其代谢产物16,17-环氧二十二碳五烯酸（16,17-EDP）对BK通道的影响。
BK通道广泛分布于SMC中，正常SMC中的BK电流占总钾电流的（64.2±2.7）%（n = 20）。DHA可激活BK通道，其半数有效浓度（EC50）为（0.23±0.03）μmol/L，然而，在用细胞色素P450环氧化酶抑制剂SKF525A孵育SMC后，DHA对BK通道的作用被消除。DHA的代谢产物16,17-EDP可重现DHA对BK通道的作用，其EC50为（19.7±2.8）nmol/L。
DHA及其代谢产物可通过激活细胞色素P450环氧化酶途径激活BK通道并扩张冠状动脉。
