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.
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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