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<html><pre>
This is the readme for the model associated with the paper
Lin MW, Wang YJ, Liu SI, Lin AA, Lo YC, Wu SN. Characterization of
aconitine- induced block of delayed rectifier K+ current in
differentiated NG108-15 neuronal cells. Neuropharmacology 2008; Feb 6;
[Epub ahead of print] (doi:10.1016/j.neuropharm.2008.01.009)
Abstract:
The effects of aconitine (ACO), a highly toxic alkaloid, on ion
currents in differentiated NG108-15 neuronal cells were investigated
in this study. ACO (0.3-30 microM) suppressed the amplitude of
delayed rectifier K+ current (IK(DR)) in a concentration-dependent
manner with an IC50 value of 3.1 microM. The presence of ACO enhanced
the rate and extent of IK(DR) inactivation, although it had no effect
on the initial activation phase of IK(DR). It could shift the
inactivation curve of IK(DR) to a hyperpolarized potential with no
change in the slope factor. Cumulative inactivation for IK(DR) was
also enhanced by ACO. Orphenadrine (30 microM) or methyllycaconitine
(30 microM) slightly suppressed IK(DR) without modifying current
decay. ACO (10 microM) had an inhibitory effect on voltage-dependent
Na+ current (INa). Under current-clamp recordings, ACO increased the
firing and widening of action potentials in these cells. With the aid
of the minimal binding scheme, the ACO actions on IK(DR) was
quantitatively provided with a dissociation constant of 0.6 microM. A
modeled cell was designed to duplicate its inhibitory effect on
spontaneous pacemaking. ACO also blocked IK(DR) in neuroblastoma
SH-SY5Y cells. Taken together, the experimental data and simulations
show that ACO can block delayed rectifier K+ channels of neurons in a
concentration- and state-dependent manner. Changes in action
potentials induced by ACO in neurons in vivo can be explained mainly
by its blocking actions on IK(DR) and INa. -------
To run the models:
XPP: start with the command
xpp ode\NG108_Acon.ode
Then select Initialconds -> Go.
This simulation will make graph similar to figure 8A in the paper of
Lin et al.
<img src="./Fig8A.JPG" alt="Figure 8A">x
From Xi vs t, changes in g_Na and ACO (microM) makes
graphis which resemble Figures 8B or 8C.
Bard Ermentrout's website http://www.pitt.edu/~phase/
describes how to get and use xpp.
These model files were submitted by:
Ming-Wei Lin, Ya-Jean Wan, An-An Lin and Sheng-Nan Wu
Institute of Basic Medical Sciences and
Department of Physiology,
National Cheng Kung University Medical Center
Tainan 70101, Taiwan
snwu@mail.ncku.edu.tw
</html></pre>