Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Cardiovasc Pharmacol. 2010 Feb;55(2):145-52. doi: 10.1097/FJC.0b013e3181ce965c.
Ephedrine (Eph) is an alkaloid extracted from the Chinese traditional medicine plant Ephedra Sinica or Ma huang, which has been known for effects on the central nervous system, cardiovascular system, and smooth muscles. However, the corresponding molecular mechanism of these effects remains unknown. In this study, we investigated the influences of Eph on heart rate, QTc interval in vivo, and the slowly activated K channels (IKs) that were composed of both KCNQ1 and KCNE1 subunits in vitro. Results demonstrated that Eph, but not pseudoephedrine, could increase the heart rate and shorten QTc interval of BALB/c mouse. Besides, Eph markedly activated cardiac IKs currents with EC50 = 50 nM and shifted G-V curves to left. But pseudoephedrine had no effects on Iks currents. The onset and offset time constants of IKs currents activated by Eph at 1 M were tauon = 49 seconds and tauoff = 400 seconds. A pair of binding sites of Eph on KCNQ1/KCNE1 channel was also shown to occur at F296 and Y299 in the S5-S6 P-loop of the KCNQ1 channel. As both amino acids are highly conserved in the KCNQ family, Eph can possibly activate other members of the KCNQ family. The mechanism of Iks activated by Eph may provide a clue for drug design in the future.
麻黄碱（Eph）是从中国传统草药麻黄或麻黄中提取的生物碱，其对中枢神经系统、心血管系统和平滑肌具有已知的作用。然而，这些作用的相应分子机制仍然未知。在这项研究中，我们研究了 Eph 对体内心率、QTc 间期的影响，以及由 KCNQ1 和 KCNE1 亚基组成的缓慢激活钾通道（IKs）在体外的影响。结果表明，Eph 而不是伪麻黄碱可增加 BALB/c 小鼠的心率并缩短 QTc 间期。此外，Eph 可显著激活心肌 IKs 电流，EC50 = 50 nM，并将 G-V 曲线向左移动。而伪麻黄碱对 Iks 电流没有影响。Eph 在 1 M 时激活 IKs 电流的起始和终止时间常数为 tauon = 49 秒和 tauoff = 400 秒。还表明 Eph 在 KCNQ1 通道的 S5-S6 P 环中的 F296 和 Y299 处对 KCNQ1/KCNE1 通道有一对 Eph 结合位点。由于这两个氨基酸在 KCNQ 家族中高度保守，Eph 可能会激活 KCNQ 家族的其他成员。Eph 激活 IKs 的机制可能为未来的药物设计提供线索。
