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Role of KCNQ1 and IKs in cardiac repolarization (Silva, Rudy 2005) (XPP)
Accession: 58581
Detailed Markov model of IKs (the slow delayed rectifier K+ current) is supplied here in XPP. The model is compared to experiment in the paper. The role of IKs in disease and drug treatments is elucidated (the prevention of excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations). See also paper authors code and reference for more and details. This XPP version of the model reproduces Figure 3C in the paper by default. These model files were submitted by: Dr. Sheng-Nan Wu, Han-Dong Chang, Jiun-Shian Wu Department of Physiology National Cheng Kung University Medical College
Reference: Silva J, Rudy Y (2005) Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve. Circulation 112:1384-91 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type:  Channel;
Brain Region(s)/Organism:  
Cell Type(s):   
Channel(s):  I K; I Potassium; KCNQ1; I_Ks;  
Gap Junctions:  
Receptor(s):  
Gene(s):  Kv1.9 Kv7.1 KCNQ1;
Transmitter(s):  Ions;
Simulation Environment:  XPP;
Model Concept(s):  Activity Patterns; Ion Channel Kinetics; Action Potentials; Heart disease; Long-QT;
Implementer(s):  Wu, Sheng-Nan [snwu at mail.ncku.edu.tw]; Chang, Han-Dong; Wu, Jiun-Shian [coolneon at gmail.com];
Search NeuronDB for information about:  I K; I Potassium; KCNQ1; I_Ks; Ions;
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IKs_Mar
readme.html
IKs_Markov_model.jpg
XPP_fig3C.jpg
IKs_Mar.ode
                            
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

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