Activation of high conductance Ca2+-activated K+ channels by sodium tanshinoneII-A sulfonate (DS-201) in porcine coronary artery smooth muscle cells
Activation of high conductance Ca2+-activated K+ channels by sodium tanshinoneII-A sulfonate (DS-201) in porcine coronary artery smooth muscle cells
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DOI：
10.1016/j.ejphar.2008.09.013
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发表时间：
2008-11-19
影响因子：
5
通讯作者：
Zeng, Xiao-Rong
中科院分区：
文献类型：
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作者：
Yang, Yan;Cai, Fang;Zeng, Xiao-Rong
血管平滑肌高电导钙激活钾通道(BKCa)通过决定膜电位水平和电压门控钙通道内钙内流，在调节血管张力中发挥重要作用。因此，改变钙通道活性或BKCa活性的药物在生理和病理条件下都会影响血管张力。丹参是丹参的干燥根，是一种常用的中药，广泛用于治疗心脑血管疾病，部分原因是由于其扩张血管的作用。丹参酮II-A磺酸钠(DS-201)是丹参酮IIA的水溶性衍生物，是丹参的主要活性成分。本研究的目的是探讨DS-201对猪冠状动脉平滑肌血管扩张作用的可能机制。DS-201对30 mM KCl收缩的冠脉平滑肌有松弛作用，这种松弛作用可被BKCa通道阻滞剂100 NM的IbTX所抑制。采用穿孔全细胞记录和单通道记录，观察DS-201对BKCa的影响。结果表明，DS-201对BKCa有激活作用。DS-201在40、80mU M全细胞构型下作用于细胞外，BKCa、宏观电流分别增加43.6%、42.1%，自发瞬时外向钾电流(STOCs)分别增加48.7%、47.4%。在由内向外的斑块上，沐浴施药20~150亩M，可使BKCa活性提高5.4~173.2倍。这些结果表明，DS-201的血管扩张作用与激活BKCa有关。(C)2008爱思唯尔B.V.保留所有权利。
High conductance Ca2+ activated K+ channels (BKCa) in vascular smooth muscles play important roles in controlling the vascular tone by determining the level of membrane potential and Ca2+ influx through voltage gated Ca2+ channels. Agents that alter the activity of Ca2+ channels or BKCa thus affect the vascular tone in both physiological and pathological conditions. Danshen, the dried root of Salvia miltiorrhiza, is a commonly used traditional Chinese medicine and is widely used as an effective remedy for cardiovascular and cerebral vascular diseases partly by its vasodilatation. Sodium tanshinoneII-A sulfonate (DS-201) is a water-soluble derivative of Tanshinone IIA, the main active component of Danshen. The purpose of this study was to explore possible mechanisms of vasodilative effects of DS-201 using porcine coronary artery smooth muscle. DS-201 induced relaxation of the coronary smooth muscle which had been contracted with 30 mM KCl, and the relaxation was inhibited by 100 nM iberiotoxin (IbTX), a specific BKCa channel blocker. Using perforated whole-cell recordings and single channel recordings, effects of DS-201 on BKCa, were examined. The results showed that DS-201 activated BKCa. Extracellular application of DS-201 at 40, 80 mu M under the whole-cell configuration induced increases of the BKCa, macroscopic currents by 43.6%, 42.1% respectively, and the spontaneous transient outward K+ currents (STOCs) by 48.7%, 47.4% respectively. In inside-out patches, bath application of 20-150 mu M of DS-201 activated BKCa, by 5.4-173.2 fold. These results indicate that the vasodilatation by DS-201 is related to activation of BKCa. (C) 2008 Elsevier B.V. All rights reserved.