This is the readme.txt for the models associated with the paper

Silva J, Rudy Y. Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve. Circulation 2005;112:1384-91. The results reproduce Figure 3C in the paper.

Abstract: BACKGROUND: The role of IKs, the slow delayed rectifier K+ current, in cardiac ventricular repolarization has been a subject of debate. METHODS AND RESULTS: We develop a detailed Markov model of IKs and its alpha-subunit KCNQ1 and examine their kinetic properties during the cardiac ventricular action potential at different rates. We observe that interaction between KCNQ1 and KCNE1 (the beta-subunit) confers kinetic properties on IKs that make it suitable for participation in action potential repolarization and its adaptation to rate changes; in particular, the channel develops an available reserve of closed states near the open state that can open rapidly on demand. CONCLUSIONS: Because of its ability to form an available reserve, IKs can function as a repolarization reserve when IKr, the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.

These kinetic parameters are shown in Data supplement of the paper:

To run the models: XPP: start with the command

xpp ode\IKs_Mar.ode

To make a trace similar to one in fig 3C of the paper: Mouse click on Initialconds, and then (G)o.

To run the full family of voltage-clamp traces, click Range over, change the value to vtest_1. Similarly set Steps:10, Start:-50, End:60, Reset Storage:N, Cycle color:y, and click Ok.

This produces a graph like:

To run deactivation protocol, please change the value to vtest_2. and then select a voltage protocol from Steps, Start and End.

Regarding xpp program, please contact with Bard Ermentrout's website http://www.pitt.edu/~phase/, which describes how to get and use xpp.

The model files were submitted by:

Dr. Sheng-Nan Wu, Han-Dong Chang, Jiun-Shian Wu Department of Physiology National Cheng Kung University Medical College Tainan 70101, Taiwan snwu@mail.ncku.edu.tw