延胡索叔胺碱和季胺碱对豚鼠心室肌细胞动作电位和HERG通道电流的影响

目的:观察延胡索叔胺碱和季胺碱对动作电位和HERG通道的影响,探讨2种生物碱抗心律失常的作用机制。方法:采用全细胞膜片钳技术记录急性分离的豚鼠心室肌细胞动作电位和培养的稳定转染HERG通道蛋白的HEK293细胞的HERG通道电流。结果:叔胺碱(30,100 mg/L)可延长APD90(90%复极化时程);1 mg/L和3 mg/L季胺碱可缩短APD90,加深静息电位;30 mg/L和100 mg/L季胺碱可延长APD90;叔胺碱(3~300 mg/L)可浓度依赖性抑制HERG尾电流幅度,IC50为55μmol/L;1 mg/L和3 mg/L季胺碱可明显升高HERG尾电流电流幅度,而30 mg/L和100 mg/L季胺碱可明显降低尾电流幅度。结论:延胡索叔胺碱可浓度依赖性延长动作电位时程和抑制HERG通道电流,而季胺碱高浓度与叔胺碱作用相同,低浓度则能够缩短动作电位时程和兴奋HERG通道电流,呈现双相性。

Effects of Tertiary Alkaloids and Quaternary Alkaloids of Rhizoma Corydalis on Action Potential in Guinea Pig Ventricular Myocytes and HERG Channel Currents

To investigate the effects of tertiary alkaloids and quaternary alkaloids of Rhizoma Corydalis on action potential and HERG channel, and to explore the mechanism of two alkaloids in anti-irrhythmia. Methods: Whole cell patch clamp technique was used to record the action potential of acutely isolated guinea pig ventricular myocytes and the HERG channel currents of cultured HEK293 cells stably transfected with HERG channel protein. Results: Tertiary alkaloids (30, 100 mg/L) could prolong APD90, and quaternary alkaloids (1, 3 mg/L) could shorten APD90 and enhance the resting potential. Quaternary alkaloids (30, 100 mg/L) prolonged APD90. Tertiary alkaloids (3-300 mg/L) inhibited HERG tail current amplitude in concentration-dependent manner. IC50 was 55 mg/L; quaternary alkaloids (1, 3 mg/L) could significantly increase HERG tail current amplitude, and quaternary alkaloids (30, 100 mg/L) could reduce the tail current amplitude. Conclusion:Corydalis tertiary alkaloids prolonged APD and inhibited HERG currents in concentration-dependent manner. Quaternary alkaloids in high concentration have the same effect as tertiary alkaloids and quaternary alkaloids in low concentration decrease APD and excite HERG currents, showing a double phase.