Li Hongliang, Shin Sung Eun, Seo Mi Seon, An Jin Ryeol, Ha Kwon-Soo, Han Eun-Taek, Hong Seok-Ho, Choi Il-Whan, Lee Dae-Sung, Yim Mi-Jin, Lee Jeong Min, Jung In Duk, Firth Amy L, Han Il Yong, Park Won Sun
Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea.
Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, South Korea.
Clin Exp Pharmacol Physiol. 2018 Feb;45(2):205-212. doi: 10.1111/1440-1681.12857. Epub 2017 Nov 8.
Amitriptyline, a tricyclic antidepressant (TCA) drug, is widely used in treatment of psychiatric disorders. However, the side effects of amitriptyline on vascular K channels remain to be determined. Therefore, we investigated the effect of the tricyclic antidepressant and serotonin reuptake inhibitor amitriptyline on voltage-dependent K (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells, using the whole-cell patch clamp technique. The Kv current amplitudes were inhibited by amitriptyline in a concentration-dependent manner, with an apparent IC value of 2.2 ± 0.14 μmol/L and a Hill coefficient of 0.87 ± 0.03. Amitriptyline shifted the activation curve to a more positive potential, but had no significant effect on the inactivation curve, suggesting that amitriptyline altered the voltage sensitivity of Kv channels. Pretreatment with Kv1.5 and Kv1.2 channel inhibitors did not alter the inhibitory effect of amitriptyline on Kv channels. Additionally, application of train pulses (1 and 2 Hz) did not affect amitriptyline-induced inhibition of Kv currents, which suggested that the action of amitriptyline on Kv channels was not use (state)-dependent. From these results, we concluded that amitriptyline inhibited the channels in a concentration-dependent, but state-independent manner.
阿米替林是一种三环类抗抑郁药（TCA），广泛用于治疗精神疾病。然而，阿米替林对血管钾通道的副作用仍有待确定。因此，我们使用全细胞膜片钳技术，研究了三环类抗抑郁药和5-羟色胺再摄取抑制剂阿米替林对新鲜分离的兔冠状动脉平滑肌细胞中电压依赖性钾（Kv）通道的影响。阿米替林以浓度依赖性方式抑制Kv电流幅度，表观半数抑制浓度（IC）值为2.2±0.14μmol/L，希尔系数为0.87±0.03。阿米替林使激活曲线向更正的电位移动，但对失活曲线无显著影响，表明阿米替林改变了Kv通道的电压敏感性。用Kv1.5和Kv1.2通道抑制剂预处理并未改变阿米替林对Kv通道的抑制作用。此外，施加串刺激（1和2Hz）并不影响阿米替林诱导的Kv电流抑制，这表明阿米替林对Kv通道的作用不依赖于使用（状态）。从这些结果中，我们得出结论，阿米替林以浓度依赖性但不依赖于状态的方式抑制通道。
