This is the readme.txt 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.
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.
For the sake of clarity, current traces were displaced in figure 2A.
Current-voltage relation of this current can also be constructed.
To run the models:
XPP: start with the command
Mouse click on Initialconds, and then (G)o.
Regarding xpp program, please contact with
Bard Ermentrout's website http://www.pitt.edu/~phase/
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.
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