初探延迟整流钾电流与药源性心律失常的关系
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摘要
目的：观察不同浓度氟哌啶醇对豚鼠单个心室肌细胞延迟整流钾离子通道电流(IK)的影响,探讨氟哌啶醇致心律失常的离子基础。方法：采用酶解法分离豚鼠心室肌细胞,应用膜片钳全细胞模式电压钳下观察不同浓度氟哌啶醇对豚鼠单个心室肌细胞延迟整流钾离子通道电流的作用,所有记录均采用相同的方案记录氟哌啶醇干预前后对延迟整流钾离子通道电流的影响。结果：在获得单个细胞后,分别给予0.3μmol·L-1、1.0μmol·L-1、3.0μmol·L-1的氟哌啶醇,延迟整流钾离子通道电流不同程度的下降；在试验电压+70mV时,延迟整流钾离子通道电流从给药前(16.6604±1.5717) pA/pF分别减少至(5.0255±1.9372) pA/pF、(9.8572±3.9002) pA/pF、(7.1794±1.816) pA/pF(n=7, P<0.01),并且0.3μmol·L-1的氟哌啶醇对延迟整流钾离子通道电流的抑制较其他两个浓度明显。结论：通过我们的研究,发现氟哌啶醇对延迟整流钾离子通道电流有抑制作用,并呈剂量依赖性。氟哌啶醇抑制了延迟整流钾离子通道电流,使动作电位时程延长而引发心律失常,氟哌啶醇致心律失常作用可能与其对钾离子通道的作用有关。
Objevtive:To investigate the effects of different concentration of haloperidol on delayed rectified potassium current(IK) in guinea pigs ventricular myocytes. Methods: Ventricular myocytes were isolated by acute enzymatic dissociation from hearts of guinea pigs. Whole-cell patch-clamp was used to observe the effects of haloperidol on delayed rectified potassium current. Results:In single ventricular myocytes of guinea pig, different concentration of haloperidol decreased IK in dose-dependent manner. Haloperidol at concentration of 0.3,1.0,3.0μmol·L-1 respectively decreased IK from (16.6604±1.5717) pA/pF to (5.0255±1.9372), (9.8572±3.9002) and (7.1794±1.816) pA/pF (n=7,P<0.01) at +70mV, and a significant decrease was observed at 0.3μmol·L-1. Conclusion: Haloperidol decreased IK in dose-dependent manner. The induced arrythmic effects of haloperidol may be related to its inhibitory effects on delayed rectified potassium current.
Objevtive:To investigate the effects of different concentration of haloperidol on delayed rectified potassium current(IK) in guinea pigs ventricular myocytes. Methods: Ventricular myocytes were isolated by acute enzymatic dissociation from hearts of guinea pigs. Whole-cell patch-clamp was used to observe the effects of haloperidol on delayed rectified potassium current. Results:In single ventricular myocytes of guinea pig, different concentration of haloperidol decreased IK in dose-dependent manner. Haloperidol at concentration of 0.3,1.0,3.0μmol·L-1 respectively decreased IK from (16.6604±1.5717) pA/pF to (5.0255±1.9372), (9.8572±3.9002) and (7.1794±1.816) pA/pF (n=7,P<0.01) at +70mV, and a significant decrease was observed at 0.3μmol·L-1. Conclusion: Haloperidol decreased IK in dose-dependent manner. The induced arrythmic effects of haloperidol may be related to its inhibitory effects on delayed rectified potassium current.
引文
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