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目的:探讨抗心律失常药物普罗帕酮对Kv1.4△N钾通道的作用,以及细胞外钾离子和pH浓度变化时对该作用的影响,并探讨该作用可能的机制。方法:将Kv1.4ΔN的mRNA注射入非洲爪蟾卵母细胞并使用双电极钳制法观察普罗帕酮对Kv1.4ΔN电生理特性的影响,以及细胞外钾离子和pH变化时的电生理特性改变。结果:pH7.4状态下,普罗帕酮对Kv1.4ΔN通道的峰电流有抑制作用,这种阻滞作用具有电压依赖性、浓度依赖性以及频率依赖性,并且随电位的升高而作用加强,符合单指数和线性关系。普罗帕酮加速电流的失活过程。在不同的钾离子浓度下,这种阻滞作用具有pH依赖性,细胞外高钾pH7.4时,不同浓度普罗帕酮灌流显示IC50为121μmol/L;细胞外酸性环境下(pH6.0)IC50提高到463μmol/L,碱性化的环境(pH8.0)降至58μmol/L。结论:普罗帕酮是Kv1.4ΔN的阻滞剂,可能与作用于细胞内的某些位点有关。
OBJECTIVE: To investigate the effect of propafenone, an anti-arrhythmic drug, on Kv1.4ΔN potassium channels, and the effect of extracellular potassium and pH on this effect, and to explore the possible mechanism. Methods: The mRNA of Kv1.4ΔN was injected into Xenopus laevis oocytes and the effect of propafenone on electrophysiological properties of Kv1.4ΔN and the change of extracellular potassium and electrophysiological characteristics during pH change were observed by double-electrode clamp . Results: Under the condition of pH7.4, propafenone inhibited the peak current of Kv1.4ΔN channel in a voltage-dependent, concentration-dependent and frequency-dependent manner, and its effect was enhanced with the increase of potential , In line with the single index and linear relationship. Propafenone accelerates the deactivation of the current. At different concentrations of potassium, the blockade was pH-dependent. At extracellular pH7.4, propafenone perfusion with different concentrations showed IC50 of 121μmol / L; extracellular acidic pH (pH 6.0) IC50 increased to 463μmol / L, alkaline environment (pH8.0) dropped to 58μmol / L. Conclusion: Propafenone is a blocker of Kv1.4ΔN, which may be related to some sites in the cell.