So Edmund Cheung, Wu Sheng-Nan, Wu Ping-Ching, Chen Hui-Zhen, Yang Chia-Jung
Department of Anesthesia, An Nan Hospital, China Medical University, Tainan City, Taiwan.
Department of Anesthesia, College of Medicine, China Medical University, Taichung, Taiwan.
Cell Physiol Biochem. 2017;41(5):2053-2066. doi: 10.1159/000475436. Epub 2017 Apr 14.
Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function.
Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH3) cells were evaluated by patch clamp techniques.
ART inhibited the amplitude of delayed-rectifier K+ current (IK(DR)) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on IK(DR) with an IC50 value of 11.2 µM and enhanced IK(DR) inactivation with a KD value of 14.7 µM. The steady-state inactivation curve of IK(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 µM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of IK(DR) in GH3 cells. ART also decreased the peak amplitude of voltage-gated Na+ current (INa) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late INa, was effective at reversing ART-induced prolongation in inactivation time constant of INa. Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs.
Under ART exposure, the inhibitory actions on both IK(DR) and INa could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.
青蒿素（ART）是一种抗疟药物，据报道会影响内分泌功能。
采用膜片钳技术评估青蒿素对垂体瘤（GH3）细胞离子电流和动作电位（APs）的影响。
青蒿素抑制延迟整流钾电流（IK(DR)）对膜去极化的反应幅度，并加速电流失活过程。它对IK(DR)有抑制作用，IC50值为11.2 μM，增强IK(DR)失活的KD值为14.7 μM。IK(DR)的稳态失活曲线向超极化方向移动了10 mV。用氯毒素（1 μM）或伊洛前列素（100 nM）预处理并未改变青蒿素对GH3细胞IK(DR)的抑制幅度。青蒿素还降低了电压门控钠电流（INa）的峰值幅度，且失活速率呈浓度依赖性减慢。应用晚期INa抑制剂KMUP-1可有效逆转青蒿素诱导的INa失活时间常数延长。在电流钳记录下，单独使用青蒿素会降低APs的幅度并延长APs的持续时间。
在青蒿素作用下，对IK(DR)和INa的抑制作用可能是该药物影响体内出现的内分泌或神经内分泌细胞膜兴奋性的潜在机制。
