Role of the calcium-independent transient outward current Ito1 in shaping action potential morphology and duration
Role of the calcium-independent transient outward current Ito1 in shaping action potential morphology and duration
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DOI：
10.1161/01.res.87.11.1026
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发表时间：
2000-11-24
影响因子：
20.1
通讯作者：
Winslow, RL
中科院分区：
文献类型：
--
作者：
Greenstein, JL;Wu, R;Winslow, RL
Kv4.3编码电流（I-Kv 4.3）是人和犬心室肌细胞电压依赖性非钙依赖性瞬时外向电流（I-to 1）的主要成分。实验证据支持I-to 1密度和1相切迹突出之间的相关性;然而，I-to 1在调节动作电位时程（APD）中的作用仍不清楚。为了帮助解决这一问题，马尔可夫状态模型的人类和犬Kv4.3和Kv1.4编码的电流在35 degreesC的基础上开发的实验测量。犬I-to 1的模型被配制为这些Kv4.3和Kv1.4电流的组合，并被纳入现有的犬心室肌细胞模型。模拟结果显示L型钙电流与I-Kv 4.3之间存在强耦合，并预测I-Kv 4.3密度与APD之间存在双峰关系，I-Kv 4.3密度的扰动可能导致APD延长或缩短，这取决于基线I-to 1电流水平。
The Kv4.3-encoded current (I-Kv4.3) has been identified as the major component of the voltage-dependent Ca2+-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 degreesC 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 Ca2+ 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.