二十二碳六烯酸增加大鼠冠状动脉平滑肌细胞大电导钙离子激活钾离子流的机制

Objective To investigate the mechanism of enhanced large conductance calciumactivated potassium channel currents (BK) in coronary smooth muscle cells (SMCs) by docosahexaenoic acid (DHA). Methods 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. Results 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 (EC50) 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 EC50 was (19.7± 2.8) nmol/L.Conclusion DHA and metabolites can activate BK channels and dilate coronary arteries through activating cytochrome P450 epoxygenase pathway.

Mechanism related to docosahexaenoic acid induced large conductance calcium-activated potassium channel currents increase in coronary smooth muscle cells