Liang Zhen-tao, Wang Xian-pei, Zeng Qiu-tang, Liao Yu-hua, Zou An-ruo, Li Lu, Tu Dan-na
Department of Cardiology, Institute of Cardiovascular Diseases, Ion Channelopathy Research Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Chin Med J (Engl). 2008 Dec 20;121(24):2584-91.
Ketanserin (KT), a selective serotonin (5-HT) 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method was used to investigate the effect of KT and potassium ion on Kv1.3 potassium channels and explore the role of blocker KT in the alteration of channel kinetics contributing to the potassium ion imbalances.
Kv1.3 channels were expressed in xenopus oocytes, and currents were measured using the two-microelectrode voltage-clamp technique.
KCl made a left shift of activation and an inactivation curve of Kv1.3 current and accelerated the activation and inactivation time constant. High extracellular [K(+)] attenuated the blockade effect of KT on Kv1.3 channels. In the presence of KT and KCl the activation and inactivation time constants were not influenced significantly no matter what was administered first. KT did not significantly inhibit Kv1.3 current induced by tetraethylammonium (TEA).
KT is a weak blocker of Kv1.3 channels at different concentrations of extracellular potassium and binds to the intracellular side of the channel pore. The inhibitor KT of ion channels is not fully effective in clinical use because of high K(+) and other electrolyte disorders.
酮色林（KT）是一种选择性5-羟色胺（5-HT）2受体拮抗剂，通过阻断外周5-HT受体的激活来降低外周血压。本研究采用电生理方法研究KT和钾离子对Kv1.3钾通道的影响，并探讨阻滞剂KT在导致钾离子失衡的通道动力学改变中的作用。
Kv1.3通道在非洲爪蟾卵母细胞中表达，采用双微电极电压钳技术测量电流。
氯化钾使Kv1.3电流的激活和失活曲线左移，并加速激活和失活时间常数。高细胞外[K(+)]减弱了KT对Kv1.3通道的阻断作用。在存在KT和氯化钾的情况下，无论先给予何种物质，激活和失活时间常数均未受到显著影响。KT对四乙铵（TEA）诱导的Kv1.3电流没有显著抑制作用。
在不同细胞外钾浓度下，KT是Kv1.3通道的弱阻滞剂，且与通道孔的胞内侧结合。由于高K(+)和其他电解质紊乱，离子通道抑制剂KT在临床应用中并不完全有效。
