Department of Electrophysiology, Institute of Cardiovasology, Luzhou Medical College, Luzhou, Sichuan, 646000, China.
Eur J Pharmacol. 2011 Apr 10;656(1-3):27-32. doi: 10.1016/j.ejphar.2011.01.028. Epub 2011 Jan 31.
Sodium tanshinone II-A sulfonate (DS-201) is a water-soluble derivative of tanshinone IIA, a main active constituent of Salvia miltiorrhiza which has been used for treatments of cardio- and cerebro-vascular diseases. DS-201 activates large conductance Ca(2+)-sensitive K(+) channels (BK(Ca)) in arterial smooth muscle cells, and reduces the vascular tone. Here we investigated the effect of DS-201 on the BK(Ca) channel kinetics by analyzing single channel currents. Smooth muscle cells were freshly isolated from mouse cerebral arteries. Single channel currents of BK(Ca) were recorded by patch clamp. DS-201 increased the total open probability (NPo) of BK(Ca) in a concentration-dependent manner. But this action required intracellular Ca(2+), and the effect depended on the Ca(2+) concentration (Ca(2+)). DS-201 activated BK(Ca) with the half maximal effective concentration (EC(50)) of 111.5μM at 0.01μM Ca(2+), and 68.5μM at 0.1μM Ca(2+) The effect of DS-201 on NPo was particularly strong in the range of Ca(2+) between 0.1 and 1μM. Analysis of the channel kinetics revealed that DS-201 had only the effect on the channel closing without affecting the channel opening, which was a striking contrast to the effect of Ca(2+), that is characterized by changing the channel opening without changing the channel closing. DS-201 may be bound to the open state of BK(Ca), and have an inhibitory effect on the transition from the open to closed state. By this way DS-201 may enhance the activity of BK(Ca), and exhibit a strong vasodilating effect against vasoconstriction in the range of Ca(2+) between 0.1 and 1μM.
丹参酮 IIA 磺酸钠（DS-201）是丹参酮 IIA 的水溶性衍生物，丹参酮 IIA 是丹参的主要活性成分，已用于治疗心脑血管疾病。DS-201 可激活动脉平滑肌细胞中的大电导钙激活钾通道（BK(Ca)），并降低血管张力。在此，我们通过分析单通道电流来研究 DS-201 对 BK(Ca)通道动力学的影响。平滑肌细胞从小鼠脑动脉中新鲜分离。通过膜片钳记录 BK(Ca)单通道电流。DS-201 以浓度依赖的方式增加 BK(Ca)的总开放概率（NPo）。但这种作用需要细胞内 Ca2+，并且作用取决于 Ca2+浓度([Ca2+]（游离）)。DS-201 以 0.01μM [Ca2+]（游离）时 EC50 为 111.5μM，0.1μM [Ca2+]（游离）时 EC50 为 68.5μM 激活 BK(Ca)。DS-201 在 0.1 和 1μM 之间的 [Ca2+]（游离）范围内对 NPo 的作用特别强。通道动力学分析表明，DS-201 仅对通道关闭有作用，而不影响通道开启，这与 [Ca2+]（游离）的作用形成鲜明对比，后者的特点是改变通道开启而不改变通道关闭。DS-201 可能与 BK(Ca)的开放状态结合，并对从开放状态向关闭状态的转变产生抑制作用。通过这种方式，DS-201 可能增强 BK(Ca)的活性，并在 0.1 和 1μM 之间的 [Ca2+]（游离）范围内对血管收缩表现出强烈的舒张作用。
