Effects of docosahexaenoic acid on large-conductance Ca2+-activated K+ channels and voltage-dependent K+ channels in rat coronary artery smooth muscle cells
Effects of docosahexaenoic acid on large-conductance Ca2+-activated K+ channels and voltage-dependent K+ channels in rat coronary artery smooth muscle cells
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DOI：
10.1038/aps.2009.7
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发表时间：
2009-03-01
影响因子：
8.2
通讯作者：
Tao, Guo
中科院分区：
文献类型：
--
作者：
Lai, Li-hong;Wang, Ru-xing;Tao, Guo
目的：观察二十二碳六烯酸(DHA)对大鼠冠状动脉平滑肌细胞(CASMCs)大电导钙激活钾通道(BKCa)和电压依赖性钾通道(K-V通道)的影响。用膜片钳技术在室温下全细胞记录单个CASMC的BKCa电流和K-V电流。结果：10、20、30、40、50、60、70和80mU/L的DHA作用于BKCa和K-V通道。结果：当DHA浓度大于10mU/L时，BKCa电流呈剂量依赖性增加。在测试电压为+80 mV时，上述浓度分别使BKCa电流增加6.1%+/-0.3%、76.5%+/-3.8%、120.6%+/-5.5%、248.0%+/-12.3%、348.7%+/-17.3%、374.2%+/-18.7%、432.2%+/-21.6%、443.1%+/-22.1%。DHA对BKCa电流的半数抑制浓度(EC_(50))为37.53+/-1.65mU·m o l/L，当DHA浓度大于20mU·m o-1/L时，K-V电流逐渐被DHA阻断。在测试电压为+50 mV时，上述不同浓度分别阻断0.40%+/-0.02%、1.37%+/-0.06%、11.80%+/-0.59%、26.50%+/-1.75%、56.50%+/-2.89%、73.30%+/-3.66%、79.70%+/-3.94%和78.1%+/-3.91%的K-V电流。DHA对K-V电流的EC50为44.20+/-0.63mU/L。结论：DHA对大鼠血管平滑肌细胞具有激活BKCa通道和阻断K-V通道的作用，DHA对BKCa通道的EC50低于对K-V通道的EC50，提示DHA对血管平滑肌细胞的舒血管作用主要是通过激活BKCa通道实现的。
Aim: To investigate the effects of docosahexaenoic acid (DHA) on large-conductance Ca2+-activated K+ (BKCa) channels and voltage-dependent K+ (K-V) channels in rat coronary artery smooth muscle cells (CASMCs).Methods: Rat CASMCs were isolated by an enzyme digestion method. BKCa and K-V currents in individual CASMCs were recorded by the patch-clamp technique in a whole-cell configuration at room temperature. Effects of DHA on BKCa and K-V channels were observed when it was applied at 10, 20, 30, 40, 50, 60, 70, and 80 mu mol/L.Results: When DHA concentrations were greater than 10 mu mol/L, BKCa currents increased in a dose-dependent manner. At a testing potential of +80 mV, 6.1%+/- 0.3%, 76.5%+/- 3.8%, 120.6%+/- 5.5%, 248.0%+/- 12.3%, 348.7%+/- 17.3%, 374.2%+/- 18.7%, 432.2%+/- 21.6%, and 443.1%+/- 22.1% of BKCa currents were increased at the above concentrations, respectively. The half-effective concentration (EC50) of DHA on BKCa currents was 37.53 +/- 1.65 mu mol/L. When DHA concentrations were greater than 20 mu mol/L, K-V currents were gradually blocked by increasing concentrations of DHA. At a testing potential of +50 mV, 0.40%+/- 0.02%, 1.37%+/- 0.06%, 11.80%+/- 0.59%, 26.50%+/- 1.75%, 56.50%+/- 2.89%, 73.30%+/- 3.66%, 79.70%+/- 3.94%, and 78.1%+/- 3.91% of K-V currents were blocked at the different concentrations listed above, respectively. The EC50 of DHA on K-V currents was 44.20 +/- 0.63 mu mol/L.Conclusions: DHA can activate BKCa channels and block K-V channels in rat CASMCs, and the EC50 of DHA for BKCa channels is lower than that for K-V channels; these findings indicate that the vasorelaxation effects of DHA on vascular smooth muscle cells are mainly due to its activation of BKCa channels.