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 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:

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