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Effect of riluzole on action potential in cultured human skeletal muscle cells (Wang YJ et al. 2008)

modeldb.science/105528

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Name		Name	Last commit message	Last commit date
Latest commit History 1 Commit
SkM_AP.JPG		SkM_AP.JPG
SkM_AP_KCa.ode		SkM_AP_KCa.ode
readme.html		readme.html

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<html><pre>
This is the readme.txt for the models associated with the paper

Wang YJ, Lin MW, Lin AA, Wu SN. Riluzole-induced block of
voltage-gated Na(+) current and activation of BK(Ca) channels in
cultured differentiated human skeletal muscle cell. 
Life Sci 2007;82:11-20

Abstract:

Riluzole is known to be of therapeutic use in the management of
amyotrophic lateral sclerosis. In this study, we investigated the
effects of riluzole on ion currents in cultured differentiated human
skeletal muscle cells (dHSkMCs). Western blotting revealed the protein
expression of alpha-subunits for both large-conductance
Ca(2+)-activated K(+) (BK(Ca)) channel and Na(+) channel (Na(v)1.5) in
these cells. Riluzole could reduce the frequency of spontaneous
beating in dHSkMCs. In whole-cell configuration, riluzole suppressed
voltage-gated Na(+) current (I(Na)) in a concentration-dependent
manner with an IC(50) value of 2.3 muM. Riluzole (10 muM) also
effectively increased Ca(2+)-activated K(+) current (I(K(Ca))) which
could be reversed by iberiotoxin (200 nM) and paxilline (1 muM), but
not by apamin (200 nM).  In inside-out patches, when applied to the
inside of the cell membrane, riluzole (10 muM) increased
BK(Ca)-channel activity with a decrease in mean closed
time. Simulation studies also unraveled that both decreased
conductance of I(Na) and increased conductance of I(K(Ca)) utilized to
mimic riluzole actions in skeletal muscle cells could combine to
decrease the amplitude of action potentials and increase the
repolarization of action potentials.  Taken together, inhibition of
I(Na) and stimulation of BK(Ca)-channel activity caused by this drug
are partly, if not entirely, responsible for its muscle relaxant
actions in clinical setting.

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To run the models:
XPP: start with the command
xpp ode\SkM_AP_K(Ca).ode

Mouse click on Initialconds, and then (G)o.
This makes a trace similar to fig 6A in the paper of Wang et al. 

<img src="./SkM_AP.JPG" alt="screenshot">

To mimic the riluzole action, changes in the parameters of gNa and
gK(Ca) will make traces similar to Fig. 6B or 6C.


Bard Ermentrout's website http://www.pitt.edu/~phase/ describes how to
get and use xpp (Bard wrote xpp).


The model file was submitted by:
Dr. Sheng-Nan Wu, Ya-Jean Wang
Natl Cheng Kung U Med Coll
Tainan 70101, Taiwan
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