Kv4.3, Kv1.4 encoded K(+) channel in heart cells (Greenstein et al 2000) (XPP)
A model of canine I:(to1) (the Ca(2+)-independent transient outward current) is formulated as the combination of 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. The model files were submitted by: Dr. Sheng-Nan Wu, Dr. Ruey J. Sung, Ya-Jean Wang and Jiun-Shian Wu e-mail: snwu@mail.ncku.edu.tw
This is the readme.txt for the models associated with the paper. Greenstein JL et al., Role of the calcium-independent transient outward current Ito1 in shaping action potential morphology and duration. Circ Res 2000;87:1026-1033. Abstract: 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. ------------------------------------- The state diagram for this model was shown in figure 1A of the paper. Model parameters are available at[. http://circres.ahajournals.org/cgi/data/87/11/1026/DC1/1](http://circres.ahajournals.org/cgi/data/87/11/1026/DC1/1) For the sake of clarity, current traces were displaced in figure 2A. Current-voltage relation of this current can also be constructed. To run the models: XPP: start with the command xpp ode\hKv4x.ode Mouse click on Initialconds, and then (G)o. Regarding xpp program, please contact with Bard Ermentrout's website <http://www.pitt.edu/~phase/> describes how to get and use xpp. To run a series of voltage-clamp studies, click Range over, change to 'vtest\_1', and then select voltage protocol from Steps (14), Start (-70) and End (+60). This makes traces: ![xpp run]([binary]) similar to fig 3A of the paper. The model files were submitted by: Dr. Sheng-Nan Wu, Dr. Ruey J. Sung, Ya-Jean Wang and Jiun-Shian Wu National Cheng Kung University Medical College Tainan 70101, Taiwan e-mail: snwu@mail.ncku.edu.tw
Joseph L. Greenstein, Richard Wu, Sunny Po, Gordon F. Tomaselli & Raimond L. Winslow. Role of the calcium-independent transient outward current I(to1) in shaping action potential morphology and duration. Circulation Research 87, 11: 1026-1033 (2000).