Greenstein J L, Wu R, Po S, Tomaselli G F, Winslow R L
Department of Biomedical Engineering, Whitaker Biomedical Engineering Institute, the Center for Computational Medicine & Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Circ Res. 2000 Nov 24;87(11):1026-33. doi: 10.1161/01.res.87.11.1026.
The Kv4.3-encoded current (I:(Kv4.3)) has been identified as the major component of the voltage-dependent Ca(2+)-independent transient outward current (I:(to1)) in human and canine ventricular cells. Experimental evidence supports a correlation between I:(to1) density and prominence of the phase 1 notch; however, the role of I:(to1) in modulating action potential duration (APD) remains unclear. To help resolve this role, Markov state models of the human and canine Kv4.3- and Kv1.4-encoded currents at 35 degrees C are developed on the basis of experimental measurements. A model of canine I:(to1) is formulated as the combination of these Kv4.3 and Kv1.4 currents and is incorporated into an existing canine ventricular myocyte model. Simulations demonstrate strong coupling between L-type Ca(2+) current and I:(Kv4.3) and predict a bimodal relationship between I:(Kv4.3) density and APD whereby perturbations in I:(Kv4.3) density may produce either prolongation or shortening of APD, depending on baseline I:(to1) current level.
Kv4.3编码电流（I:(Kv4.3)）已被确定为人类和犬类心室细胞中电压依赖性、钙非依赖性瞬时外向电流（I:(to1)）的主要成分。实验证据支持I:(to1)密度与1期切迹突出程度之间存在相关性；然而，I:(to1)在调节动作电位时程（APD）中的作用仍不清楚。为了帮助阐明这一作用，基于实验测量结果，建立了35摄氏度时人类和犬类Kv4.3及Kv1.4编码电流的马尔可夫状态模型。将犬类I:(to1)模型构建为这些Kv4.3和Kv1.4电流的组合，并将其纳入现有的犬类心室肌细胞模型。模拟结果表明L型钙电流与I:(Kv4.3)之间存在强耦合，并预测I:(Kv4.3)密度与APD之间存在双峰关系，即I:(Kv4.3)密度的扰动可能导致APD延长或缩短，这取决于基线I:(to1)电流水平。
