Models that contain the Implementer : Huang, Chin-Wei

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    Models   Description
1.  Effects of eugenol on the firing of action potentials in NG108-15 neurons (Huang et al. 2011)
"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 voltage-gated 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)). ... 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. ... 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."
2.  Simulation studies on mechanisms of levetiracetam-mediated inhibition of IK(DR) (Huang et al. 2009)
Levetiracetam (LEV) is an S-enantiomer pyrrolidone derivative with established antiepileptic efficacy in generalized epilepsy and partial epilepsy. However, its effects on ion currents and membrane potential remain largely unclear. In this study, we investigated the effect of LEV on differentiated NG108-15 neurons. ... Simulation studies in a modified Hodgkin-Huxley neuron and network unraveled that the reduction of slowly inactivating IK(DR) resulted in membrane depolarization accompanied by termination of the firing of action potentials in a stochastic manner. Therefore, the inhibitory effects on slowly inactivating IK(DR) (Kv3.1-encoded current) may constitute one of the underlying mechanisms through which LEV affects neuronal activity in vivo.
3.  Squid axon (Hodgkin, Huxley 1952) used in (Chen et al 2010) (R language)
"... Previous work showed that magnetic electrical field-induced antinoceptive action is mediated by activation of capsaicin-sensitive sensory afferents. In this study, a modified Hodgkin-Huxley model, in which TRP-like current (I-TRP) was incorporated, was implemented to predict the firing behavior of action potentials (APs), as the model neuron was exposed to sinusoidal changes in externally-applied voltage. ... Our simulation results suggest that modulation of TRP-like channels functionally expressed in small-diameter peripheral sensory neurons should be an important mechanism through which it can contribute to the firing pattern of APs."
4.  The role of ATP-sensitive potassium channels in a hippocampal neuron (Huang et al. 2007)
"Hyperglycemia-related neuronal excitability and epileptic seizures are not uncommon in clinical practice. However, their underlying mechanism remains elusive. ATP-sensitive K(+) (K(ATP)) channels are found in many excitable cells, including cardiac myocytes, pancreatic beta cells, and neurons. These channels provide a link between the electrical activity of cell membranes and cellular metabolism. We investigated the effects of higher extracellular glucose on hippocampal K(ATP) channel activities and neuronal excitability. The cell-attached patch-clamp configuration on cultured hippocampal cells and a novel multielectrode recording system on hippocampal slices were employed. In addition, a simulation modeling hippocampal CA3 pyramidal neurons (Pinsky-Rinzel model) was analyzed to investigate the role of K(ATP) channels in the firing of simulated action potentials. ..."
5.  Zonisamide-induced inhibition of the firing of APs in hippocampal neurons (Huang et al. 2007)
Zonisamide (ZNS), a synthetic benzisoxazole derivative, has been used as an alternative choice in the treatment of epilepsy with a better efficacy and safety profile. However, little is known regarding the mechanism of ZNS actions on ion currents in neurons. We thus investigated its effect on ion currents in differentiated hippocampal 19-7 cells. The ZNS (30 uM) reversibly increased the amplitude of K+ outward currents and paxilline (1 uM) was effective in suppressing ZNS-induced increase of K+ outward currents. In inside-out configuration, ZNS (30 uM) applied to the intracellular face of the membrane did not alter single-channel conductance; however, it did enhance the activity of large-conductance Ca2+-activated K+ (BKCa) channels primarily by decreasing mean closed time. The EC50 value for ZNS-stimulated BKCa channels was 34 uM. This drug caused a left shift in the activation curve of BKCa channels with no change in the gating charge of these channels. ZNS at a concentration greater than 100 uM also reduced the amplitude of A-type K+ current in these cells. A simulation modeling based on hippocampal CA3 pyramidal neurons (Pinsky-Rinzel model) was also analyzed to investigate the inhibitory effect of ZNS on the firing of simulated action potentials. Taken together, this study suggests that in hippocampal neurons, during the exposure to ZNS, the ZNS-mediated effects on BKCa channels and IA could be one of the ionic mechanisms through which it affects neuronal excitability.

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