Integration: a method for evaluating voltage-dependent transient outward potassium currents in pharmacology / 中国药理学与毒理学杂志

ABSTRACT

AIM To evaluate the integration method for analysis of voltage-dependent Ca2+-independent transient outward K+ currents (Ito) in pharmacology. METHODSThe inactivation phases of Ito were best fitted by the sum of two or three exponentials equations. The area under the raw current curves (AUC) was obtained by the integration of exponential equations. The AUC normalized to the cell capacitance represented the net K+ charge flow during any depolarized duration and was as the index for comparison. Calcineurin overexpression transgenic (TG) mice showed downregulation of Ito. These data were tested by the integration method. RESULTS AUC obtained from three or two exponentials fittings was calculated as: AUC=A1τ1+A2τ2+A3τ3+A0t-A1τ1e-t/τ1-A2τ2e-t/τ2-A3τ3e-t/τ3 or AUC=A1τ1+A2τ2+A0t-A1τ1e-t/τ1-A2τ2e-t/τ2. The 50% and 90% action potential duration (APD50, APD90) in ventricular myocytes of mice are about 10 ms and 30 ms, respectively. AUC at 10 ms (AUC50, AUC of 50% APD) and 30 ms (AUC90, AUC of 90% APD) in left ventricle cardiomyocytes of wild type (WT) and TG mice were normalized to the cell capacitance. The normalized AUC50 and AUC90 of WT group were significantly more than those of TG group, which was consistent to the prolongation of APD in TG mice and the previous published results(downregulation of components of Ito in TG mice). CONCLUSION The integration method was an ideal way for analysis of transient outward K+ currents in pharmacology.