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Standardized README to Markdown format #2

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# Readme 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.

## How 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 Bard Ermentrout's website [http://www.pitt.edu/~phase/](http://www.pitt.edu/~phase/) which 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.

![xpp run](hKv4x.jpg)

## Contact

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

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2025-05-27 – Standardized to Markdown
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