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.
The results reproduce Figure 3C in the paper.
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
To run the models:
XPP: start with the command
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