Effects of antiarrhythmic drugs on the hyperpolarization-activated cyclic nucleotide-gated channel current.
Effects of antiarrhythmic drugs on the hyperpolarization-activated cyclic nucleotide-gated channel current.
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DOI：
10.1254/jphs.08312fp
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发表时间：
2009
影响因子：
3.5
通讯作者：
Atsushi Tamura;T. Ogura;H. Uemura;Y. Reien;T. Kishimoto;T. Nagai;I. Komuro;M. Miyazaki;H. Nakaya
中科院分区：
文献类型：
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作者：
Atsushi Tamura;T. Ogura;H. Uemura;Y. Reien;T. Kishimoto;T. Nagai;I. Komuro;M. Miyazaki;H. Nakaya
在心律失常抑制试验报告后，提出了Sicilian Gambit的表格框架，以显示抗心律失常药物对离子通道和受体的作用，为心律失常的药物治疗提供更合理的方法。然而，由于抗心律失常药物对If的影响尚未被彻底研究，我们使用膜片钳技术来确定各种抗心律失常药物对HCN（超极化激活环核苷酸门控）通道电流的影响。HCN4通道是心脏中HCN通道的显性亚型，在HEK293细胞中表达。胺碘酮和贝地尔对HCN4通道电流的抑制作用，IC50值分别为4.5和4.9微米，接近其治疗浓度。奎尼丁、双帕酰胺、齐苯喹啉、利多卡因、美西汀、阿普林定、普罗帕酮、氟卡奈、心得安、维拉帕米在其治疗浓度下对HCN4通道电流的抑制作用较弱，IC50值分别为78.3、249、46.8、276、309、43.7、14.3、1700、50.5和44.9 microM，提示临床对If的抑制作用较小。D、L-Sotalol对HCN4通道电流影响不大。关于许多抗心律失常药物的hcn4通道效应的信息可能有助于确定治疗各种心律失常的适当药物，同时尽量减少不良反应。
After the report of the Cardiac Arrhythmia Suppression Trial, a tabular framework of the Sicilian Gambit has been proposed to display actions of antiarrhythmic drugs on ion channels and receptors and to provide more rational pharmacotherapy of arrhythmias. However, because effects of antiarrhythmic drugs on If have not been thoroughly examined, we used patch clamp techniques to determine the effects of various antiarrhythmic drugs on the HCN (hyperpolarization-activated cyclic nucleotide-gated) channel currents. HCN4 channels, a dominant isoform of HCN channels in the heart, were expressed in HEK293 cells. Amiodarone and bepridil potently inhibited the HCN4 channel current with IC50 values of 4.5 and 4.9 microM, respectively, which were close to their therapeutic concentrations. The inhibitory effects of quinidine, disopyramide, cibenzoline, lidocaine, mexiletine, aprindine, propafenone, flecainide, propranolol, and verapamil on the HCN4 channel current were weak in their therapeutic concentrations, with IC50 values of 78.3, 249, 46.8, 276, 309, 43.7, 14.3, 1700, 50.5, and 44.9 microM, respectively, suggesting that the inhibitory effects on If would be clinically small. D,L-Sotalol hardly affected the HCN4 channel current. Information about the HCN4-channel effects of many antiarrhythmic drugs may be useful for determining the appropriate drug for treatment of various arrhythmias while minimizing adverse effects.