This is the readme.txt for the model associated with the paper.
Huang CW, Chow JC, Tsai JJ, Wu SN. Characterizing the effects of
eugenol on neuronal ionic currents and hyperexcitability.
Psychopharmacology 2011; Dec 13; [Epub ahead of print]
Rationale: Eugenol (EUG, 4-allyl-2-methoxyphenol), the main component
of essential oil extracted from cloves, has various uses in medicine
because of its potential to modulate neuronal excitability. However,
its effects on the ionic mechanisms remains incompletely understood.
Objectives: We aimed to investigate EUG's effects on neuronal ionic
currents and excitability, especially on voltagegated ion currents,
and to verify the effects on a hyperexcitability-temporal lobe seizure
model. Methods With the aid of patch-clamp technology, we first
investigated the effects of EUG on ionic currents in NG108-15 neuronal
cells differentiated with cyclic AMP. We then used modified
Pinsky-Rinzel simulation modeling to evaluate its effects on
spontaneous action potentials (APs). Finally, we investigated its
effects on pilocarpine-induced seizures in rats. Results: EUG
depressed the transient and late components of INa in the neurons. It
not only increased the degree of INa inactivation, but specifically
suppressed the non-inactivating INa (INa(NI)). Its inhibition of
INa(NI) was reversed by tefluthrin. In addition, EUG diminished
L-type Ca2+ current and delayed rectifier K+ current only at higher
concentrations. EUG's effects on APs frequency reduction was
verified by the simulation modeling. In pilocarpine-induced seizures,
the EUG-treated rats showed no shorter seizure latency but a lower
seizure severity and mortality than the control rats. The EUG's
effect on seizure severity was occluded by the INa(NI) antagonist
riluzole. Conclusion: The synergistic blocking effects of INa and
INa(NI) contributes to the main mechanism through which EUG affects
the firing of neuronal APs and modulate neuronal hyperexcitability
such as pilocarpine-induced temporal lobe seizures.
To run the model; XPP: start with the command
This simulation will make a graph similar to figure 6. Notably, press
Initialconds -> Go
and then get the results (Vs, Ina and Ina_in) in the left side of
Figure 6 in the paper of Huang et al. Then press File Get par Set to
change to EUG parameter set file, eugenol effects on the firing of
action potentials shown in the right side of Figure 6 in that paper.
Bard Ermentrout's website available at http://www.pitt.edu/~phase/
describes how to get and use xpp.
This model file was submitted by:
Department of Physiology
National Cheng Kung University Medical College
Tainan City, Taiwan