| | Models | Description |
| 1. |
A model for pituitary GH(3) lactotroph (Wu and Chang 2005)
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The ATP-sensitive K(+) (K(ATP)) channels are composed of sulfonylurea receptor and inwardly rectifying K(+) channel (Kir6.2) subunit. These channels are regulated by intracellular ADP/ATP ratio and play a role in cellular metabolism. ... The objective of this study was to determine whether Diethyl pyrocarbonate (DEPC) modifies K(ATP)-channel activity in pituitary GH(3) cells. ... Simulation studies also demonstrated that the increased conductance of K(ATP)-channels used to mimic DEPC actions reduced the frequency of spontaneous action potentials and fluctuation of intracellular Ca(2+). The results indicate that chemical modification with DEPC enhances K(ATP)-channel activity and influences functional activities of pituitary GH(3) cells. See paper for more and details. |
| 2. |
Action potential of adult rat ventricle (Wang et al. 2008)
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"Aconitine (ACO), a highly toxic diterpenoid alkaloid, is recognized to have effects
on cardiac voltage-gated Na(+) channels. However, it remains unknown whether it has
any effects on K(+) currents. The effects of ACO on ion currents in differentiated
clonal cardiac (H9c2) cells and in cultured neonatal rat ventricular myocytes were
investigated in this study. ..." The rat action potential in this simulation was played back into the cell for experiments reported in this paper. |
| 3. |
Action potential of striated muscle fiber (Adrian et al 1970)
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1. Membrane currents during step depolarizations were determined by
a method in which three electrodes were inserted near the end of a
fibre in the frog's sartorius muscle. The theoretical basis and
limitations of the method are discussed.
2. Measurements of the membrane capacity (CM) and resting resistance
(RM) derived from the current during a step change in membrane
potential are consistent with values found by other methods.
3. In fibres made mechanically inactive with hypertonic solutions
(Ringer solution plus 350 mM sucrose) step depolarizations produced
ionic currents which resembled those of nerve in showing (a) an early
transient inward current, abolished by tetrodotoxin, which reversed
when the depolarization was carried beyond an internal potential of
about +20 mV, (b) a delayed outward current, with a linear instantaneous
current¡Xvoltage relation, and a mean equilibrium potential with a normal
potassium concentration (2¡P5 mM) of -85 mV.
4. The reversal potential for the early current appears to be consistent
with the sodium equilibrium potential expected in hypertonic solutions.
5. The variation of the equilibrium potential for the delayed current
(V¡¬K) with external potassium concentration suggests that the channel
for delayed current has a ratio of potassium to sodium permeability of
30:1; this is less than the resting membrane where the ratio appears
to be 100:1. V¡¬K corresponds well with the membrane potential at the
beginning of the negative after-potential observed under similar conditions.
6. The variation of V¡¬K with the amount of current which has passed
through the delayed channel suggests that potassium ions accumulate in a
space of between 1/3 and 1/6 of the fibre volume. If potassium accumulates in
the transverse tubular system (T system) much greater variation in V¡¬K
would be expected.
7. The delayed current is not maintained but is inactivated like the early
current. The inactivation is approximately exponential with a time constant
of 0¡P5 to 1 sec at 20¢X C. The steady-state inactivation of the potassium
current is similar to that for the sodium current, but its voltage
dependence is less steep and the potential for half inactivation is 20 mV
rate more positive.
8. Reconstructions of ionic currents were made in terms of the parameters
(m, n, h) of the Hodgkin¡XHuxley model for the squid axon, using constants
which showed a similar dependence on voltage.
9. Propagated action potentials and conduction velocities were computed for
various conditions on the assumption that the T system behaves as if it were
a series resistance and capacity in parallel with surface capacity and the
channels for sodium, potassium and leak current. There was reasonable
agreement with observed values, the main difference being that the
calculated velocities and rates of rise were somewhat less than those
observed experimentally. |
| 4. |
Actions of Rotenone on ionic currents and MEPPs in Mouse Hippocampal Neurons (Huang et al 2018)
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" ... With the aid of patch-clamp technology and simulation modeling,
the effects of (Rotenone) Rot on membrane ion currents present in
mHippoE-14 cells were investigated. Results: Addition of Rot produced
an inhibitory action on the peak amplitude of INa ...; however,
neither activation nor inactivation kinetics of INa was changed during
cell exposure to this compound. Addition of Rot produced little or no
modifications in the steady-state inactivation curve of INa. Rot
increased the amplitude of Ca2+-activated Cl- current in response to
membrane depolarization ... . Moreover, when these cells were exposed
to 10 µM Rot, a specific population of ATP-sensitive K+ channels
... was measured, despite its inability to alter single-channel
conductance. Under current clamp condition, the frequency of miniature
end-plate potentials in mHippoE-14 cells was significantly raised in
the presence of Rot (10 µM) with no changes in their amplitude and
time course of rise and decay. In simulated model of hippocampal
neurons incorporated with chemical autaptic connection, increased
autaptic strength to mimic the action of Rot was noted to change the
bursting pattern with emergence of subthreshold
potentials. Conclusions: The Rot effects presented herein might exert
a significant action on functional activities of hippocampal neurons
occurring in vivo. " |
| 5. |
Allosteric gating of K channels (Horrigan et al 1999)
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Calcium sensitive large-conductance K channel conductance is controlled by both cytoplasmic calcium and membrane potential.
Experimental data obtained by the inside out patch method can be understood in terms of a gating scheme where a central transition between a closed and an open conformation is allosterically regulated by the state of four independent and identical voltage sensors. See paper for more and details. |
| 6. |
Ca(2+) oscillations based on Ca-induced Ca-release (Dupont et al 1991)
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We consider a simple, minimal model for signal-induced Ca2+ oscillations based on Ca(2+)-induced Ca2+ release. The model takes into account the existence of two pools of intracellular Ca2+, namely, one sensitive to inositol 1,4,5 trisphosphate (InsP3) whose synthesis is elicited by the stimulus, and one insensitive to InsP3. See paper for more and details. |
| 7. |
Ca-dependent K Channel: kinetics from rat muscle (Moczydlowski, Latorre 1983) XPP
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This is an XPP version of the classic KCa channel from Moczydlowski and Latorre 1983. |
| 8. |
Cardiac action potential based on Luo-Rudy phase 1 model (Luo and Rudy 1991), (Wu 2004)
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A mathematical model of the membrane action potential of the mammalian
ventricular cell is introduced. The model is based, whenever possible,
on recent single-cell and single-channel data and incorporates the
possibility of changing extracellular potassium concentration [K]o. The
fast sodium current, INa, is characterized by fast upstroke velocity (Vmax
= 400 V/sec) and slow recovery from inactivation. The time-independent
potassium current, IK1, includes a negative-slope phase and displays
significant crossover phenomenon as [K]o is varied. The time-dependent
potassium current, IK, shows only a minimal degree of crossover. A novel
potassium current that activates at plateau potentials is included in
the model. The simulated action potential duplicates the experimentally
observed effects of changes in [K]o on action potential duration and rest
potential. See papers for more and details. |
| 9. |
Cardiac Atrial Cell (Courtemanche et al 1998) (C++)
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The mechanisms underlying many important properties of the human atrial action potential (AP)
are poorly understood. Using specific formulations of the K+, Na+, and Ca2+ currents based on
data recorded from human atrial myocytes, along with representations of pump, exchange, and
background currents, we developed a mathematical model of the AP. The model AP resembles APs
recorded from human atrial samples and responds to rate changes, L-type Ca2+ current blockade,
Na+/Ca2+ exchanger inhibition, and variations in transient outward current amplitude in a
fashion similar to experimental recordings. Rate-dependent adaptation of AP duration, an
important determinant of susceptibility to atrial fibrillation, was attributable to
incomplete L-type Ca2+ current recovery from inactivation and incomplete delayed rectifier
current deactivation at rapid rates. Experimental observations of variable AP morphology
could be accounted for by changes in transient outward current density, as suggested
experimentally. We conclude that this mathematical model of the human atrial AP reproduces
a variety of observed AP behaviors and provides insights into the mechanisms of clinically
important AP properties.
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| 10. |
Consequences of HERG mutations in the long QT syndrome (Clancy, Rudy 2001)
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This study demonstrates which mutations can prolong APD sufficiently to generate early
afterdepolarizations (EADs), which may trigger life-threatening arrhythmias. The severity of the phenotype is shown to
depend on the specific kinetic changes and how they affect I(Kr) during the time course of the action potential. See paper for more and details.
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| 11. |
Contribution of ATP-sensitive potassium channels in the neuronal network (Huang et al. 2009)
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Epileptic seizures in diabetic hyperglycemia (DH) are not uncommon.
This study aimed to determine the acute behavioral, pathological, and electrophysiological effects of status epilepticus (SE) on diabetic animals.
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We also used a simulation model to evaluate intracellular adenosine triphosphate (ATP) and neuroexcitability.
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In the simulation, increased intracellular ATP concentration promoted action potential firing.
This finding that rats with DH had more brain damage after SE than rats without diabetes suggests the importance of intensively treating hyperglycemia and seizures in diabetic patients with epilepsy. |
| 12. |
Effect of riluzole on action potential in cultured human skeletal muscle cells (Wang YJ et al. 2008)
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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. |
| 13. |
Effect of slowly inactivating IKdr to delayed firing of action potentials (Wu et al. 2008)
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"The properties of slowly inactivating delayed-rectifier K+ current (IKdr) were investigated in NG108-15 neuronal cells differentiated with long-term exposure to dibutyryl cyclic AMP.
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The computer model, in which state-dependent inactivation of IKdr was incorporated, was also implemented to predict the firing behavior present in NG108-15 cells.
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Our theoretical work and the experimental results led us to propose a pivotal role of slowly inactivating IKdr in delayed firing of APs in NG108-15 cells. The results also suggest that aconitine modulation of IKdr gating is an important molecular mechanism through which it can contribute to neuronal firing." |
| 14. |
Effect of trp-like current on APs during exposure to sinusoidal voltage (Chen et al. 2010)
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"...
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.
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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." |
| 15. |
Effects of eugenol on the firing of action potentials in NG108-15 neurons (Huang et al. 2011)
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"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.
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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." |
| 16. |
HERG K+ channels spike-frequency adaptation (Chiesa et al 1997)
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Spike frequency adaptation has contributions from the IHERG current (encoded by the human eag-related gene
(HERG); Warmke & Ganetzky, 1994), which develops with
slow kinetics during depolarization and contributes to the
repolarization of the long action potentials typically present
in the heart. IHERG is one of the delayed rectifier currents
(IK(r)) of the heart, and HERG mutations are associated
with one of the cardiac arrhythmia LQT syndromes (LQT2).
See paper for more and details.
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| 17. |
Kv4.3, Kv1.4 encoded K(+) channel in heart cells (Greenstein et al 2000) (XPP)
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A model of canine I:(to1) (the Ca(2+)-independent transient outward current) is formulated as the combination of Kv4.3 and Kv1.4
currents and is incorporated into an existing canine ventricular myocyte model. Simulations demonstrate strong
coupling between L-type Ca(2+) current and I:(Kv4.3) and predict a bimodal relationship between I:(Kv4.3)
density and APD whereby perturbations in I:(Kv4.3) density may produce either prolongation or shortening of APD,
depending on baseline I:(to1) current level.
The model files were submitted by:
Dr. Sheng-Nan Wu, Dr. Ruey J. Sung, Ya-Jean Wang and Jiun-Shian Wu
e-mail: snwu@mail.ncku.edu.tw
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| 18. |
Markovian model for cardiac sodium channel (Clancy, Rudy 2002)
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Complex physiological interactions determine the functional consequences of gene abnormalities and make mechanistic interpretation of phenotypes extremely difficult. A recent example is a single mutation in the C terminus of the cardiac Na(+) channel, 1795insD. The mutation causes two distinct clinical syndromes, long QT (LQT) and Brugada, leading to life-threatening cardiac arrhythmias. Coexistence of these syndromes is seemingly paradoxical; LQT is associated with enhanced Na(+) channel function, and Brugada with reduced function. Using a computational approach, we demonstrate that the 1795insD mutation exerts variable effects depending on the myocardial substrate. We develop Markov models of the wild-type and 1795insD cardiac Na(+) channels. See reference for more and details. The model files were submitted by: Dr. Jiun-Shian Wu, Dr. Sheng-Nan Wu, Dr. Ruey J. Sung, Han-Dong Chang. |
| 19. |
Markovian model for SCN8A-encoded channel (Kuo et al 2020)
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Sesamin (SSM) and sesamolin (SesA) are the two major furofuran lignans of sesame oil and they have been previously noticed to exert various biological actions. However, their modulatory actions on different types of ionic currents in electrically excitable cells remain largely unresolved. The present experiments were undertaken to explore the possible perturbations of SSM and SesA on different types of ionic currents, e.g., voltage-gated Na+ currents (INa), erg-mediated K+ currents (IK(erg)), M-type K+ currents (IK(M)), delayed-rectifier K+ currents (IK(DR)) and hyperpolarization-activated cation currents (Ih) identified from pituitary tumor (GH3) cells. The exposure to SSM or SesA depressed the transient and late components of INa with different potencies. The IC50 value of SSM needed to lessen the peak or sustained INa was calculated to be 7.2 or 0.6 µM, while that of SesA was 9.8 or 2.5 µM, respectively. The dissociation constant of SSM-perturbed inhibition on INa, based on the first-order reaction scheme, was measured to be 0.93 µM, a value very similar to the IC50 for its depressant action on sustained INa. The addition of SSM was also effective at suppressing the amplitude of resurgent INa. The addition of SSM could concentration-dependently inhibit the IK(M) amplitude with an IC50 value of 4.8 µM. SSM at a concentration of 30 µM could suppress the amplitude of IK(erg), while at 10 µM, it mildly decreased the IK(DR) amplitude. However, the addition of neither SSM (10 µM) nor SesA (10 µM) altered the amplitude or kinetics of Ih in response to long-lasting hyperpolarization. Additionally, in this study, a modified Markovian model designed for SCN8A-encoded (or NaV1.6) channels was implemented to evaluate the plausible modifications of SSM on the gating kinetics of NaV channels. The model demonstrated herein was well suited to predict that the SSM-mediated decrease in peak INa, followed by increased current inactivation, which could largely account for its favorable decrease in the probability of the open-blocked over open state of NaV channels. Collectively, our study provides evidence that highlights the notion that SSM or SesA could block multiple ion currents, such as INa and IK(M), and suggests that these actions are potentially important and may participate in the functional activities of various electrically excitable cells in vivo. |
| 20. |
Markovian model for single-channel recordings of Ik_1 in ventricular cells (Matsuoka et al 2003)
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The interaction between many currents in a cardiac ventricular model are examined in this paper. One of the main contributions come from a current called IK_1. An XPP version of this model was supplied by
Hsieng-Jung Lai, Jiun-Shian Wu, Sheng-Nan Wu, Ruey J. Sung, Han-Dong
Chang. Please see paper and model for more and details. |
| 21. |
Prediction for the presence of voltage-gated Ca2+ channels in myelinated central axons (Brown 2003)
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"The objective of this current study was to investigate whether voltage gated Ca(2+) channels are present
on axons of the adult rat optic nerve (RON).
Simulations of axonal excitability using a Hodgkin-Huxley based
one-compartment model incorporating I(Na), I(K) and leak currents were used to predict conditions under
which the potential contribution of a Ca(2+) current to an evoked action potential could be measured.
... , as predicted by the simulation, reducing the repolarizing effect of I(K) by adding the
K(+) channel blocker 4-AP revealed a Ca(2+) component on the repolarizing phase of the action potential that
was blocked by the Ca(2+) channel inhibitor nifedipine."
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| 22. |
Properties of aconitine-induced block of KDR current in NG108-15 neurons (Lin et al. 2008)
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"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). ... A modeled cell was designed to duplicate its inhibitory effect on spontaneous pacemaking. ... 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." |
| 23. |
Role of KCNQ1 and IKs in cardiac repolarization (Silva, Rudy 2005) (XPP)
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Detailed Markov model of IKs (the slow delayed rectifier K+ current) is supplied here in XPP. The model is compared to experiment in the paper. The role of IKs in disease and drug treatments is elucidated (the prevention of excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations). See also modeldb accession number 55748 code and reference for more and details. This XPP version of the model reproduces Figure 3C in the paper by default.
These model files were submitted by: Dr. Sheng-Nan Wu, Han-Dong Chang, Jiun-Shian Wu
Department of Physiology
National Cheng Kung University Medical College
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| 24. |
Simulation studies on mechanisms of levetiracetam-mediated inhibition of IK(DR) (Huang et al. 2009)
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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. |
| 25. |
Simulation study of Andersen-Tawil syndrome (Sung et al 2006)
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Patients with Andersen-Tawil syndrome (ATS) mostly have mutations on the KCNJ2 gene producing loss of function or
dominant-negative suppression of the inward rectifier K(+) channel Kir2.1. However, clinical manifestations of ATS
including dysmorphic features, periodic paralysis (hypo-, hyper-, or normokalemic), long QT, and ventricular arrhythmias
(VA) are considerably variable. Using a modified dynamic Luo-Rudy simulation model of cardiac ventricular myocyte, we
elucidate the mechanisms of VA in ATS. We adopted a kinetic model of KCNJ2 in which channel block by Mg(+2) and
spermine was incorporated. In this study, we attempt to examine the effects of KCNJ2 mutations on the ventricular action
potential (AP), single-channel Markovian models were reformulated and incorporated into the dynamic Luo-Rudy model
for rapidly and slowly delayed rectifying K(+) currents and KCNJ2 channel. During pacing at 1.0 Hz with [K(+)]o at 5.4
mM, a stepwise 10% reduction of Kir2.1 channel conductance progressively prolonged the terminal repolarization phase
of AP along with gradual depolarization of the resting membrane potential (RMP). At 90% reduction, early after-
depolarizations (EADs) became inducible and RMP was depolarized to -55.0 mV (control: -90.1 mV) followed by
emergence of spontaneous action potentials (SAP). Both EADs and SAP were facilitated by a decrease in [K(+)]o and
suppressed by increase in [K(+)]o. beta-adrenergic stimulation enhanced delayed after-depolarizations (DADs) and could
also facilitate EADs as well as SAP in the setting of low [K(+)]o and reduced Kir2.1 channel conductance. In conclusion,
the spectrum of VA in ATS includes (1) triggered activity mediated by EADs and/or DADs, and (2) abnormal automaticity
manifested as SAP. These VA can be aggravated by a decrease in [K(+)]o and beta-adrenergic stimulation, and may
potentially induce torsades de pointes and cause sudden death. In patients with ATS, the hypokalemic form of periodic
paralysis should have the highest propensity to VA especially during physical activities. |
| 26. |
Spike trains in Hodgkin–Huxley model and ISIs of acupuncture manipulations (Wang et al. 2008)
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The Hodgkin-Huxley equations (HH) are parameterized by a number of parameters
and shows a variety of qualitatively different behaviors depending on the
parameter values. Under stimulation of an external periodic voltage, the
ISIs (interspike intervals) of a HH model are investigated in this work,
while the frequency of the voltage is taken as the controlling parameter.
As well-known, the science of acupuncture and moxibustion is an important
component of Traditional Chinese Medicine with a long history. Although there
are a number of different acupuncture manipulations, the method for
distinguishing them is rarely investigated. With the idea of ISI, we study
the electrical signal time series at the spinal dorsal horn produced by
three different acupuncture manipulations in Zusanli point and present an
effective way to distinguish them.
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| 27. |
Spontaneous calcium oscillations in astrocytes (Lavrentovich and Hemkin 2008)
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" ... We propose here a mathematical model of how spontaneous Ca2+
oscillations arise in astrocytes. This model uses the calcium-induced calcium release and inositol cross-coupling
mechanisms coupled with a receptor-independent method for producing inositol (1,4,5)-trisphosphate as the heart
of the model. By computationally mimicking experimental constraints we have found that this model provides
results that are qualitatively similar to experiment." |
| 28. |
Squid axon (Hodgkin, Huxley 1952) used in (Chen et al 2010) (R language)
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"... 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." |
| 29. |
Synergistic inhibitory action of oxcarbazepine on INa and IK (Huang et al. 2008)
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"Oxcarbazepine (OXC), one of the newer anti-epileptic drugs, has been demonstrating its efficacy on wide-spectrum neuropsychiatric disorders.
... 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 ... caused a reversible reduction in the amplitude of voltage-gated Na+ current (INa) ...
and produce(d) a significant prolongation in the recovery of INa inactivation.
...
Moreover, OXC could suppress the amplitude of delayed rectifier K+ current (IK(DR)), with no effect on M-type K+ current (IK(M)).
...
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."
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| 30. |
The role of ATP-sensitive potassium channels in a hippocampal neuron (Huang et al. 2007)
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"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. ..." |
| 31. |
Ventricular cell model (Luo Rudy dynamic model) (Luo Rudy 1994) used in (Wang et al 2006) (XPP)
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A mathematical model of the membrane action potential of the mammalian ventricular cell introduced in Luo, Rudy 1991 and used in Wang et al 2006 is made available here in XPP. The model is based, whenever possible, on recent single-cell and single-channel data and incorporates the possibility of changing extracellular potassium concentration [K]o. ... The results are consistent with recent experimental observations, and the model simulations relate these phenomena to the underlying ionic channel kinetics. See papers for more and details. |
| 32. |
Zonisamide-induced inhibition of the firing of APs in hippocampal neurons (Huang et al. 2007)
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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. |
