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Synergistic inhibitory action of oxcarbazepine on INa and IK (Huang et al. 2008)

modeldb.science/114450

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Name		Name	Last commit message	Last commit date
Latest commit History 1 Commit
Neuron_OXC.ode		Neuron_OXC.ode
neuron_OXC.JPG		neuron_OXC.JPG
readme.html		readme.html

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This is the readme for th model associated with the papers:

1. Huang et al., The synergistic inhibitory actions of oxcarbazepine
   on voltage- gated sodium and potassium currents in differentiated
   NG108-15 neuronal cells and model neurons. Int J
   Neuropsychopharmacol 2008;11:597-610.

Abstract:

Oxcarbazepine (OXC), one of the newer anti-epileptic drugs, has been
demonstrating its efficacy on wide-spectrum neuropsychiatric
disorders. However, the ionic mechanism of OXC actions in neurons
remains incompletely understood. With the aid of patch-clamp
technology, we first investigated the effects of OXC on ion currents
in NG108-15 neuronal cells differentiated with cyclic AMP. We found
OXC (0.3-30 mum) caused a reversible reduction in the amplitude of
voltage-gated Na+ current (INa).  The IC50 value required for the
inhibition of INa by OXC was 3.1 mum. OXC (3 mum) could shift the
steady-state inactivation of INa to a more negative membrane potential
by approximately -9 mV with no effect on the slope of the inactivation
curve, and produce a significant prolongation in the recovery of INa
inactivation.  Additionally, OXC was effective in suppressing
persistent INa (INa(P)) elicited by long ramp pulses. The blockade of
INa by OXC does not simply reduce current magnitude, but alters
current kinetics. Moreover, OXC could suppress the amplitude of
delayed rectifier K+ current (IK(DR)), with no effect on M-type K+
current (IK(M)). In current-clamp configuration, OXC could reduce the
amplitude of action potentials and prolong action-potential
duration. Furthermore, the simulations, based on hippocampal pyramidal
neurons (Pinsky-Rinzel model) and a network of the Hodgkin-Huxley
model, were analysed to investigate the effect of OXC on action
potentials. Taken together, our results suggest that the synergistic
blocking effects on INa and IK(DR) may contribute to the underlying
mechanisms through which OXC affects neuronal function in vivo.


To run the model:
Expand the archive and cd into the newly created directory and run:
xppaut neuron_oxc.ode
then click on Initialcond -> Go
The potential trace is shown in the lower part of Figure 9b in the paper of 
Huang et al (2008):

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

The model file was supplied by:

Dr. Sheng-Nan Wu
National Cheng Kung University Medical College
Tainan 70101, Taiwan
snwu@mail.ncku.edu.tw
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