氯苄律定对豚鼠心肌细胞钾通道的抑制作用

Effect of Chlorobenzyltetrahydroberberine on Potassium Channels in Isolated Guinea Pig Ventricular Myocytes

氯苄律定是四氢小檗碱的衍生物，具有抗心律失常作用，常规电生理发现其延长ＡＰＤ５０及减少心肌钾的丢失，本文研究它对心肌钾通道的影响。采用膜片钳全细胞记录的方法，研究氯苄律定对豚鼠心肌钾离子通道的作用。氯苄律定在３μｍｏｌ／Ｌ，１０μｍｏｌ／Ｌ和３０μｍｏｌ／Ｌ抑制延迟整流钾电流分别为１５．７％±２．４％，３６％±３％，５９％±６％，同样浓度下对内向整流钾通道无明显抑制作用。氯苄律定抗心律失常作用与抑制延迟整流钾通道有关。

In the routine electrophysiology, we found that chlorobenzyltetrahydroberberine prolonged the APD50 and depleted the potassium collection outside the cell. For the purpose of detecting chlorobenzyltetrahydroberberine principle of action, we examined the effects of chlorobenzyltetrahydroberberine on both wholecell inward rectifier potassium current(Ik1) and delayed outward potassium current(Ik) in isolated guinea pig ventricular myocytes using patchclamp techniques. Chlorobenzyltetrahydroberberine was found to reduce the delayed outward current in guinea pig ventricular myocytes when cells were depolarized by holding potential from -40 mV to +50 mV. After blocking Ca2+ inward current with CdCl2 100 μmol/L. Ik current can be recorded. Chlorobenzyltetrahydroberberine 3 μmol/L inhibited the Ik 30%±4%(P<005), chlorobenzyltetrahydroberberine 3 μmol/L inhibited the Ikail apparently 157%±24%(P<005), 10 μmol/L 36%±3%(P<001), and 30 μmol/L 59%±6%(P<0001), whereas the inward rectifier current(Ik1), was not changed by chlorobenzyltetrahydroberberine from 3, 10, 30 μmol/L. Chlorobenzyltetrahydroberberine had no effect on the IV relationship of the inward rectifier potassium current. These results suggest that the APD50 prolongation induced by chlorobenzyltetrahydroberberine was likely due to the Ik blocking effects. Chlorobenzyltetrahydroberberine was therefore a selective K+ channel blocking agent with showing class Ⅲ antiarrhythmic properties.