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目的 评价一种药理学中分析电压依赖性瞬时外向钾电流 (Ito)的积分方法。方法 Ito的失活相可被 2指数或 3指数方程拟合。原始电流曲线下面积 (AUC)可通过指数方程积分获得。以细胞膜电容标准化后的曲线下面积表示除极化时程中钾离子的净通量 ,作为比较指标。钙调磷酸酶过表达转基因鼠心肌细胞表现Ito下调 ,此数据用于验证Ito的积分分析方法的可靠性。结果 AUC可通过 3指数或2指数方程的积分公式获得 :AUC =A1τ1+A2 τ2 +A3τ3+A0 t -A1τ1e-t/τ1-A2 τ2 e-t/τ2 -A3τ3e-t/τ3或AUC =A1τ1+A2 τ2 +A0 t-A1τ1e-t/τ1-A2 τ2 e-t/τ2 。小鼠心室肌 5 0 %和 90 %动作电位时程分别约为 10ms和 30ms。将Ito0～ 10ms (AUC50 )和 0～ 30ms(AUC90 )的曲线下面积以细胞膜电容进行标准化。野生型鼠心肌细胞的AUC50 和AUC90 明显高于钙调磷酸酶过表达转基因鼠 ,此结果与转基因鼠心室肌细胞动作电位时程延长相一致 ,与前期发表结果一致 (钙调磷酸酶过表达转基因鼠心肌细胞Ito各成分下调 )。结论 积分法是药理学中一种简便准确的分析Ito的方法。
OBJECTIVE: To evaluate an integral method for the analysis of voltage-dependent transient outward potassium currents (Ito) in pharmacology. The deactivated phase of method Ito can be fitted with a 2 or 3 exponential equation. The area under the original current curve (AUC) can be obtained by exponential integration. The area under the curve normalized to the cell membrane capacitance represents the net flux of potassium ions during depolarization as a comparison indicator. Calcineurin overexpression in transgenic rat cardiomyocytes showed Ito downregulation, and this data was used to verify the reliability of the Ito integral analysis method. The result AUC can be obtained by the integral formula of the 3 or 2 exponential equation: AUC = A1τ1 + A2 τ2 + A3τ3 + A0 t -A1τ1e -t / τ1-A2 τ2 et / τ2 -A3τ3e -t / τ3 or AUC = A1τ1 + A2 τ2 + A0 t-A1τ1e-t / τ1-A2 τ2 et / τ2. Mouse ventricular muscle 50% and 90% action potential duration were about 10ms and 30ms. The area under the curve of Ito 0-10 ms (AUC50) and 0-30 ms (AUC90) was normalized to the cell membrane capacitance. The AUC50 and AUC90 of wild-type mouse cardiomyocytes were significantly higher than that of calcineurin overexpression transgenic mice, which was consistent with the prolongation of the action potential duration of transgenic rat ventricular myocytes, consistent with the previous published results (calcineurin overexpression transgene Rat cardiac myocytes Ito down regulation). Conclusion The integral method is a simple and accurate method for the analysis of Ito in pharmacology.