二十二碳六烯酸对大鼠冠状动脉平滑肌细胞离子通道的影响

Effects of docosahexaenoic acid on ion channels of rat coronary artery smooth muscle cells

目的探讨二十二碳六烯酸（DHA）对大鼠冠状动脉平滑肌细胞大电导钙激活性钾通道电流（IBKCa）和电压依赖性钾通道电流（IKv）的动力学影响，阐述DHA舒张血管的机制。方法采用膜片钳技术在全细胞模式下，记录0、10、20、40、60和80μmol／L的DHA对大鼠冠状动脉平滑肌细胞上IBKCa和IKv的影响。结果（1）DHA可呈浓度依赖性地增加IBKCa和BKCa尾电流，对IBKCa稳态激活无影响。在指令电压＋150mV，不同浓度DHA（0、10、20、40、60和80μmol／L）作用下，IBKCa电流密度分别为（68．2±22．8）、（72．4±24．5）、（120．4±37．9）、（237．5±53．2）、（323．6±74．8）和（370．6±88．2）pA／pF（P〈0．05，n=30）。DHA对IBKCa的半效作用浓度（EC50）为（36．22±2．17）μmol／L。（2）DHA对IKv和Kv尾电流呈浓度依赖性抑制，使IKv稳态激活曲线右移、稳态失活曲线左移。在指令电压＋50mV，不同浓度DHA（0、10、20、40、60和80μmol／L）作用下，IKv电流密度分别为（43．9±2．3）、（43．8±2．3）、（42．9±2．0）、（32．3±1．9）、（11．7±1．5）和（9．6±1．2）pA／pF（P〈0．05，／7,=30）。DHA对IKv的EC50为（44．19±0．63）μmol／L。结论DHA对BKc。通道有激活作用，对Kv通道有抑制作用。DHA舒张血管的作用是对血管平滑肌细胞BKCa及Kv通道综合作用的结果。

Objective To investigate the effects of docosahexaenoic acid （DHA） on large- conductance Ca2＋ -activated K ＋ （BKca） channels and voltage-dependent K ＋ （Kv ）channels in rat coronary artery smooth muscle cells （ CASMCs ） , and evaluate the vasorelaxation mechanisms of DHA. Methods BKca and Kv currents in individual CASMC were recorded by patch-clamp technique in whole-cell configuration. Effects of DHA at various concentrations （0, 10, 20, 40, 60 and 80 μmol/L） on BKca and Kv channels were observed. Results （1） DHA enhanced IBKca and BKca tail currents in a concentration- dependent manner while did not affect the stably activated curves of IBKca. IBKca current densities were （68.2±22.8）, （72.4±24.5）, （120.4±37.9）, （237.5±53.2）, （323.6±74.8）and （370.6±88.2） pA/pF respectively （P 〈0. 05, n =30） with the addition of 0, 10, 20, 40, 60 and 80 μmot/L DHA concentration, and half-effect concentration （ECs0） of DHA was （36.22 ±2. 17）μmol/L. （2） IKv and Kv tail currents were gradually reduced, stably activated curves of IKv were shift to the right, and stably inactivated curves were shifted to the left in the presence of DHA. IKv current densities were （43.9 ± 2. 3 ） , （43.8±2.3）, （42.9±2.0）, （32.3±1.9）, （11.7±1.5） and （9.6±1.2）pA/pF respectively（P〈 0. 05, n = 30） post treatment with 0, 10, 20, 40, 60 and 80 μmol/L DHA under manding potential equal to ＋ 50 mV, and EC50 of DHA was （44. 19 ± 0. 63 ） μmol/L. Conclusion DHA can activate BKc~ channels and block Kv channels in rat CASMCs, the combined effects on BKc, and Kv channels lead to the vasodilation effects of DHA on vascular smooth muscle cells.