Models that contain the Model Type : Channel/Receptor

(The model addresses properties of an ion channel or receptor (some receptors are also ion channels).)
Re-display model names without descriptions
    Models   Description
1. 3D model of the olfactory bulb (Migliore et al. 2014)
This entry contains a link to a full HD version of movie 1 and the NEURON code of the paper: "Distributed organization of a brain microcircuit analysed by three-dimensional modeling: the olfactory bulb" by M Migliore, F Cavarretta, ML Hines, and GM Shepherd.
2. A model of beta-adrenergic modulation of IKs in the guinea-pig ventricle (Severi et al. 2009)
Detailed understanding of IKs gating complexity may provide clues on the mechanisms of cardiac repolarization instability and the resulting arrhythmias. We developed and tested a kinetic Markov model to interpret physiologically relevant IKs properties, including pause-dependency and modulation by beta-adrenergic receptors (beta-AR). The model was developed from the Silva & Rudy formulation. Parameters were optimized on control and ISO experimental data, respectively.
3. A nicotinic acetylcholine receptor kinetic model (Edelstein et al. 1996)
Nicotinic acetylcholine receptors are transmembrane oligomeric proteins that mediate interconversions between open and closed channel states under the control of neurotransmitters. .. In order to represent the functional properties of such receptors, we have developed a kinetic model that links conformational interconversion rates to agonist binding and extends the general principles of the Monod- Wyman-Changeux model of allosteric transitions. ... Application of the model to the peripheral nicotinic acetylcholine receptor (nAChR) accounts for the main properties of ligand-gating, including single-channel events, and several new relationships are predicted. ... In terms of future developments, the analysis presented here provides a physical basis for constructing more biologically realistic models of synaptic modulation that may be applied to artificial neural networks.
4. A single kinetic model for all human voltage-gated sodium channels (Balbi et al, 2017)
Code for simulating macroscopic currents of sodium channels (Nav1.1. to Nav1.9), by means of a single kinetic model. Intensity-voltage curves, normalized conductance-voltage relationship, steady-state availability and recovery from inactivation are simulated.
5. Action Potential initiation and backpropagation in Neocortical L5 Pyramidal Neuron (Hu et al. 2009)
"...Previous computational studies have yielded conflicting conclusions about the role of Na+ channel density and biophysical properties in action potential initiation as a result of inconsistent estimates of channel density. Our modeling studies integrated the immunostaining and electrophysiological results and showed that the lowest threshold for action potential initiation at the distal AIS was largely determined by the density of low-threshold Nav1.6 channels ... Distinct from the function of Nav1.6 channel, the Nav1.2 channel may control action potential backpropagation because of its high density at the proximal AIS and high threshold. ... In conclusion, distal AIS accumulation of Nav1.6 channels determines the low threshold for action potential initiation; whereas proximal AIS accumulation of Nav1.2 channels sets the threshold for the generation of somatodendritic potentials and ensures action potential backpropagation to the soma and dendrites. Thus, Nav1.6 and Nav1.2 channels serve distinct functions in action potential initiation and backpropagation."
6. Allosteric gating of K channels (Horrigan et al 1999)
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.
7. An allosteric kinetics of NMDARs in STDP (Urakubo et al. 2008)
"... We developed a detailed biophysical model of STDP and found that the model required spike timing-dependent distinct suppression of NMDARs by Ca2+-calmodulin. This led us to predict an allosteric kinetics of NMDARs: a slow and rapid suppression of NMDARs by Ca2+-calmodulin with prespiking -> postspiking and postspiking -> prespiking, respectively. We found that the allosteric kinetics, but not the conventional kinetics, is consistent with specific features of amplitudes and peak time of NMDAR-mediated EPSPs in experiments. ..." See paper for more and details.
8. Availability of low-threshold Ca2+ current in retinal ganglion cells (Lee SC et al. 2003)
"... we measured T-type current of isolated goldfish retinal ganglion cells with perforated-patch voltageclamp methods in solutions containing a normal extracellular Ca2+ concentration. The voltage sensitivities and rates of current activation, inactivation, deactivation, and recovery from inactivation were similar to those of expressed +1G (CaV3.1) Ca2+ channel clones, except that the rate of deactivation was significantly faster. We reproduced the amplitude and kinetics of measured T currents with a numerical simulation based on a kinetic model developed for an +1G Ca2+ channel. Finally, we show that this model predicts the increase of T-type current made available between resting potential and spike threshold by repetitive hyperpolarizations presented at rates that are within the bandwidth of signals processed in situ by these neurons."
9. BCM-like synaptic plasticity with conductance-based models (Narayanan Johnston, 2010)
" ... Although the BCM-like plasticity framework has been a useful formulation to understand synaptic plasticity and metaplasticity, a mechanism for the activity-dependent regulation of this modification threshold has remained an open question. In this simulation study based on CA1 pyramidal cells, we use a modification of the calcium-dependent hypothesis proposed elsewhere and show that a change in the hyperpolarization-activated, nonspecific-cation h current is capable of shifting the modification threshold. ..."
10. Biologically Constrained Basal Ganglia model (BCBG model) (Lienard, Girard 2014)
We studied the physiology and function of the basal ganglia through the design of mean-field models of the whole basal ganglia. The parameterizations are optimized with multi-objective evolutionary algorithm to respect best a collection of numerous anatomical data and electrophysiological data. The main outcomes of our study are: • The strength of the GPe to GPi/SNr connection does not support opposed activities in the GPe and GPi/SNr. • STN and MSN target more the GPe than the GPi/SNr. • Selection arises from the structure of the basal ganglia, without properly segregated direct and indirect pathways and without specific inputs from pyramidal tract neurons of the cortex. Selection is enhanced when the projection from GPe to GPi/SNr has a diffuse pattern.
11. Ca+/HCN channel-dependent persistent activity in multiscale model of neocortex (Neymotin et al 2016)
"Neuronal persistent activity has been primarily assessed in terms of electrical mechanisms, without attention to the complex array of molecular events that also control cell excitability. We developed a multiscale neocortical model proceeding from the molecular to the network level to assess the contributions of calcium regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in providing additional and complementary support of continuing activation in the network. ..."
12. Ca-dependent K Channel: kinetics from rat muscle (Moczydlowski, Latorre 1983) NEURON
Macroscopic channel model based on Moczydlowski, E. and Latorre, R. (1983). Gating kinetics of Ca++ activated K+ channels from rat muscle incorporated into planar lipid bilayers. J. Gen. Physiol. 82: 511-542 See README file for more information.
13. Ca-dependent K Channel: kinetics from rat muscle (Moczydlowski, Latorre 1983) XPP
This is an XPP version of the classic KCa channel from Moczydlowski and Latorre 1983.
14. CA1 interneuron: K currents (Lien et al 2002)
NEURON mod files for slow and fast K-DR, and K-A potassium currents in inhibitory interneurones of stratum oriens-alveus of the hippocampal CA1 region.
15. CA1 pyramidal neuron: Dendritic Na+ spikes are required for LTP at distal synapses (Kim et al 2015)
This model simulates the effects of dendritic sodium spikes initiated in distal apical dendrites on the voltage and the calcium dynamics revealed by calcium imaging. It shows that dendritic sodium spike promotes large and transient calcium influxes via NMDA receptor and L-type voltage-gated calcium channels, which contribute to the induction of LTP at distal synapses.
16. CA1 pyramidal neuron: effects of R213Q and R312W Kv7.2 mutations (Miceli et al. 2013)
NEURON mod files from the paper: Miceli et al, Genotype–phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of Kv7.2 potassium channel subunits, PNAS 2013 Feb 25. [Epub ahead of print] In this paper, functional studies revealed that in homomeric or heteromeric configuration with KV7.2 and/or KV7.3 subunits, R213W and R213Q mutations markedly destabilized the open state, causing a dramatic decrease in channel voltage sensitivity. Modeling these channels in CA1 hippocampal pyramidal cells revealed that both mutations increased cell firing frequency, with the R213Q mutation prompting more dramatic functional changes compared with the R213W mutation.
17. CA1 pyramidal neuron: functional significance of axonal Kv7 channels (Shah et al. 2008)
The model used in this paper confirmed the experimental findings suggesting that axonal Kv7 channels are critically and uniquely required for determining the inherent spontaneous firing of hippocampal CA1 pyramids, independently of alterations in synaptic activity. The model predicts that the axonal Kv7 density could be 3-5 times that at the soma.
18. CA1 pyramidal neuron: Ih current (Migliore et al. 2012)
NEURON files from the paper: Migliore M, Migliore R (2012) Know Your Current Ih: Interaction with a Shunting Current Explains the Puzzling Effects of Its Pharmacological or Pathological Modulations. PLoS ONE 7(5): e36867. doi:10.1371/journal.pone.0036867. Experimental findings on the effects of Ih current modulation, which is particularly involved in epilepsy, appear to be inconsistent. In the paper, using a realistic model we show how and why a shunting current, such as that carried by TASK-like channels, dependent on the Ih peak conductance is able to explain virtually all experimental findings on Ih up- or down-regulation by modulators or pathological conditions.
19. CA1 pyramidal neurons: effects of Alzheimer (Culmone and Migliore 2012)
The model predicts possible therapeutic treatments of Alzheimers's Disease in terms of pharmacological manipulations of channels' kinetic and activation properties. The results suggest how and which mechanism can be targeted by a drug to restore the original firing conditions. The simulations reproduce somatic membrane potential in control conditions, when 90% of membrane is affected by AD (Fig.4A of the paper), and after treatment (Fig.4B of the paper).
20. Ca2+ current versus Ca2+ channel cooperativity of exocytosis (Matveev et al. 2009)
"... While varying extracellular or intracellular Ca2+ concentration assesses the intrinsic biochemical Ca2+ cooperativity of neurotransmitter release, varying the number of open Ca2+ channels using pharmacological channel block or the tail current titration probes the cooperativity between individual Ca2+ channels in triggering exocytosis. ... Here we provide a detailed analysis of the Ca2+ sensitivity measures probed by these experimental protocols, present simple expressions for special cases, and demonstrate the distinction between the Ca2+ current cooperativity, defined by the relationship between exocytosis rate and the whole-terminal Ca2+ current magnitude, and the underlying Ca2+ channel cooperativity, defined as the average number of channels involved in the release of a single vesicle. ... Further, we use three-dimensional computational modeling of buffered Ca2+ diffusion to analyze these distinct Ca2+ cooperativity measures, and demonstrate the role of endogenous Ca2+ buffers on such measures. We show that buffers can either increase or decrease the Ca2+ current cooperativity of exocytosis, depending on their concentration and the single-channel Ca2+ current."
21. CA3 Radiatum/Lacunosum-Moleculare interneuron, Ih (Anderson et al. 2011)
"The present study examines the biophysical properties and functional implications of Ih in hippocampal area CA3 interneurons with somata in strata radiatum and lacunosum-moleculare.... The functional consequences of Ih were examined with regard to temporal summation and impedance measurements. ... From impedance measurements, we found that Ih did not confer theta-band resonance, but flattened the impedance–frequency relations instead. ... Finally, a model of Ih was employed in computational analyses to confirm and elaborate upon the contributions of Ih to impedance and temporal summation."
22. Calcium waves and mGluR-dependent synaptic plasticity in CA1 pyr. neurons (Ashhad & Narayanan 2013)
A morphologically realistic, conductance-based model equipped with kinetic schemes that govern several calcium signalling modules and pathways in CA1 pyramidal neurons
23. Cardiac action potential based on Luo-Rudy phase 1 model (Luo and Rudy 1991), (Wu 2004)
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.
24. Cell signaling/ion channel variability effects on neuronal response (Anderson, Makadia, et al. 2015)
" ... We evaluated the impact of molecular variability in the expression of cell signaling components and ion channels on electrophysiological excitability and neuromodulation. We employed a computational approach that integrated neuropeptide receptor-mediated signaling with electrophysiology. We simulated a population of neurons in which expression levels of a neuropeptide receptor and multiple ion channels were simultaneously varied within a physiological range. We analyzed the effects of variation on the electrophysiological response to a neuropeptide stimulus. ..."
25. Channel parameter estimation from current clamp and neuronal properties (Toth, Crunelli 2001)
In this paper, we present a method by which the activation and kinetic properties of INa, IK can be estimated from current-clamp data, more precisely from the time course of the action potential, provided some additional electrophysiological properties of the neurone are a priori known. See reference for details and more.
26. CN Octopus Cell: Ih current (Bal, Oertel 2000)
NEURON mod files for the Ih current from the paper R. Bal and D. Oertel Hyperpolarization-Activated, Mixed-Cation Current (Ih) in Octopus Cells of the Mammalian Cochlear Nucleus, J. Neurophysiol. 84, 806-817 (2000). Contact if you have any questions about the implementation of the model.
27. Computational modelling of channelrhodopsin-2 photocurrent characteristics (Stefanescu et al. 2013)
The codes are directly related with the results presented in the manuscript; in brief, it is a computational investigation on the effects of optogenetic actuation on excitatory and inhibitory neurons when 3- and 4- state model is used to implement the ChR2 kinetics. Different parameters of optostimulation are investigated and the results compared with experimental data previously published by other research groups.
28. Consequences of HERG mutations in the long QT syndrome (Clancy, Rudy 2001)
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.
29. Dentate granule cell: mAHP & sAHP; SK & Kv7/M channels (Mateos-Aparicio et al., 2014)
The model is based on that of Aradi & Holmes (1999; Journal of Computational Neuroscience 6, 215-235). It was used to help understand the contribution of M and SK channels to the medium afterhyperpolarization (mAHP) following one or seven spikes, as well as the contribution of M channels to the slow afterhyperpolarization (sAHP). We found that SK channels are the main determinants of the mAHP, in contrast to CA1 pyramidal cells where the mAHP is primarily caused by the opening of M channels. The model reproduced these experimental results, but we were unable to reproduce the effects of the M-channel blocker XE991 on the sAHP. It is suggested that either the XE991-sensitive component of the sAHP is not due to M channels, or that when contributing to the sAHP, these channels operate in a mode different from that associated with the mAHP.
30. DG granule cell: I-A model (Beck et al 1992)
NEURON mod files for the I-A current from the paper: Beck H, Ficker E, Heinemann U. Properties of two voltage-activated potassium currents in acutely isolated juvenile rat dentate gyrus granule cells. J. Neurophysiol. 68, 2086-2099 (1992) Contact if you have any questions about the implementation of the model.
31. Effect of slowly inactivating IKdr to delayed firing of action potentials (Wu et al. 2008)
"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. ... 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. ... 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."
32. 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."
33. Efffect of propofol on potassium current in cardiac H9c2 cells (Liu et al. 2008)
"... The effects of propofol, an intravenous anesthetic agent with a distinct chemical structure, on ion currents of differentiated clonal cardiac (H9c2) cells were investigated in this study. Propofol ... suppressed the amplitude of delayed rectifier K(+) current (I(K(DR))) in a concentration-dependent manner with an IC(50) value of 36 muM. ... Propofol (30 muM) had no effect on erg-mediated K(+) current in these cells; however, it suppressed L-type Ca(2+) current (I(Ca,L)) of cardiac and skeletal types to a similar extent. ... Numerical simulations of I(K(DR)) based on a Markovian model reproduce the experimental results and show that propofol-induced blockade of I(K(DR)) is associated with an decrease in forward rate of the activation process and an increase in transitional rate into the inactivated state. ..."
34. Elementary mechanisms producing facilitation of Cav2.1 (P/Q-type) channels
"The regulation of Ca(V)2.1 (P/Q-type) channels by calmodulin (CaM) showcases the powerful Ca(2+) decoding capabilities of CaM in complex with the family of Ca(V)1-2 Ca(2+) channels. Throughout this family, CaM does not simply exert a binary on/off regulatory effect; rather, Ca(2+) binding to either the C- or N-terminal lobe of CaM alone can selectively trigger a distinct form of channel modulation. ... Ca(2+) binding to the C-terminal lobe induces Ca(2+)-dependent facilitation of opening (CDF), whereas the N-terminal lobe yields Ca(2+)-dependent inactivation of opening (CDI). ... Furthermore, direct single-channel determinations of channel open probability (P(o)) and kinetic simulations demonstrate that CDF represents a genuine enhancement of open probability, without appreciable change of activation kinetics. This enhanced-opening mechanism suggests that the CDF evoked during action-potential trains would produce not only larger, but longer-lasting Ca(2+) responses, an outcome with potential ramifications for short-term synaptic plasticity."
35. Endocannabinoid dynamics gate spike-timing dependent depression and potentiation (Cui et al 2016)
The endocannabinoid (eCB) system is considered involved in synaptic depression. Recent reports have also linked eCBs to synaptic potentiation. However it is not known how eCB signaling may support such bidirectionality. To question the mechanisms of this phenomena in spike-timing dependent plasticity (STDP) at corticostriatal synapses, we combined electrophysiology experiments with biophysical modeling. We demonstrate that STDP is controlled by eCB levels and dynamics: prolonged and moderate levels of eCB lead to eCB-mediated long-term depression (eCB-tLTD) while short and large eCB transients produce eCB-mediated long-term potentiation (eCB-tLTP). Therefore, just like neurotransmitters glutamate or GABA, eCB form a bidirectional system.
36. Evaluation of stochastic diff. eq. approximation of ion channel gating models (Bruce 2009)
Fox and Lu derived an algorithm based on stochastic differential equations for approximating the kinetics of ion channel gating that is simpler and faster than "exact" algorithms for simulating Markov process models of channel gating. However, the approximation may not be sufficiently accurate to predict statistics of action potential generation in some cases. The objective of this study was to develop a framework for analyzing the inaccuracies and determining their origin. Simulations of a patch of membrane with voltage-gated sodium and potassium channels were performed using an exact algorithm for the kinetics of channel gating and the approximate algorithm of Fox & Lu. ... The results indicate that: (i) the source of the inaccuracy is that the Fox & Lu algorithm does not adequately describe the combined behavior of the multiple activation particles in each sodium and potassium channel, and (ii) the accuracy does not improve with increasing numbers of channels.
37. Experimental and modeling studies of desensitization of P2X3 receptors (Sokolova et al. 2006)
"The function of ATP-activated P2X3 receptors involved in pain sensation is modulated by desensitization, a phenomenon poorly understood. The present study used patch-clamp recording from cultured rat or mouse sensory neurons and kinetic modeling to clarify the properties of P2X3 receptor desensitization. ... Desensitization properties were well accounted for by a cyclic model in which receptors could be desensitized from either open or closed states. Recovery was assumed to be a multistate process with distinct kinetics dependent on the agonist-dependent dissociation rate from desensitized receptors. ... By using subthreshold concentrations of an HAD (high-affinity desensitization)-potent agonist, it might be possible to generate sustained inhibition of P2X3 receptors for controlling chronic pain."
38. Febrile seizure-induced modifications to Ih (Chen et al 2001)
Modeling and experiments in the paper Chen K,Aradi I, Thom N,Eghbal-Ahmadi M, Baram TZ, and Soltesz I (2001) support the hypothesis that modified Ih currents strongly influence inhibitory inputs in CA1 cells and that the depolarizing shift in Ih activation plays a primary role in this process. Please see the paper for details. Some modeling details are available at Correspondance should be addressed to (modeling was done by Ildiko Aradi,
39. Gap junction coupled network of striatal fast spiking interneurons (Hjorth et al. 2009)
Gap junctions between striatal FS neurons has very weak ability to synchronise spiking. Input uncorrelated between neighbouring neurons is shunted, while correlated input is not.
40. Globus pallidus neuron models with differing dendritic Na channel expression (Edgerton et al., 2010)
A set of 9 multi-compartmental rat GP neuron models (585 compartments) differing only in their expression of dendritic fast sodium channels were compared in their synaptic integration properties. Dendritic fast sodium channels were found to increase the importance of distal synapses (both excitatory AND inhibitory), increase spike timing variability with in vivo-like synaptic input, and make the model neurons highly sensitive to clustered synchronous excitation.
41. HMM of Nav1.7 WT and F1449V (Gurkiewicz et al. 2011)
Neuron mod files for the WT and F1449V Na+ currents from the paper: Kinetic Modeling of Nav1.7 Provides Insight Into Erythromelalgia-associated F1449V Mutation M. Gurkiewicz, A. Korngreen, S. Waxman, and A. Lampert. J.Neurophysiol. (2011). The parameters for the K65, K53 and K63 transitions were derived from microscopic reversibility relationships in the model.
42. Hodgkin-Huxley model of persistent activity in PFC neurons (Winograd et al. 2008) (NEURON python)
The paper demonstrate a form of graded persistent activity activated by hyperpolarization. This phenomenon is modeled based on a slow calcium regulation of Ih, similar to that introduced earlier for thalamic neurons (see Destexhe et al., J Neurophysiol. 1996). The only difference is that the calcium signal is here provided by the high-threshold calcium current (instead of the low-threshold calcium current in thalamic neurons).
43. Hodgkin-Huxley model of persistent activity in prefrontal cortex neurons (Winograd et al. 2008)
The paper demonstrate a form of graded persistent activity activated by hyperpolarization. This phenomenon is modeled based on a slow calcium regulation of Ih, similar to that introduced earlier for thalamic neurons (see Destexhe et al., J Neurophysiol. 1996). The only difference is that the calcium signal is here provided by the high-threshold calcium current (instead of the low-threshold calcium current in thalamic neurons).
44. Hodgkin-Huxley models of different classes of cortical neurons (Pospischil et al. 2008)
"We review here the development of Hodgkin- Huxley (HH) type models of cerebral cortex and thalamic neurons for network simulations. The intrinsic electrophysiological properties of cortical neurons were analyzed from several preparations, and we selected the four most prominent electrophysiological classes of neurons. These four classes are 'fast spiking', 'regular spiking', 'intrinsically bursting' and 'low-threshold spike' cells. For each class, we fit 'minimal' HH type models to experimental data. ..."
45. Hodgkin–Huxley model with fractional gating (Teka et al. 2016)
We use fractional order derivatives to model the kinetic dynamics of the gate variables for the potassium and sodium conductances of the Hodgkin-Huxley model. Our results show that power-law dynamics of the different gate variables result in a wide range of action potential shapes and spiking patterns, even in the case where the model was stimulated with constant current. As a consequence, power-law behaving conductances result in an increase in the number of spiking patterns a neuron can generate and, we propose, expand the computational capacity of the neuron.
46. Hypocretin and Locus Coeruleus model neurons (Carter et al 2012)
Conductance based model of the hypocretin neurons (HCRT) and another one of the Locus Coeruleus one (LC). The HCRT drive the LCs via the HCRT receptor on the LCs. The LCs lead to the awakening of the mice if the number of spikes raises over 10 spikes in 10 seconds window.
47. Hysteresis in voltage gating of HCN channels (Elinder et al 2006, Mannikko et al 2005)
We found that HCN2 and HCN4 channels expressed in oocytes from the frog Xenopus laevis do not display the activation kinetic changes that we (previously) observed in spHCN and HCN1. However, HCN2 and HCN4 channels display changes in their tail currents, suggesting that these channels also undergo mode shifts and that the conformational changes underlying the mode shifts are due to conserved aspects of HCN channels. With computer modelling, we show that in channels with relatively slow opening kinetics and fast mode-shift transitions, such as HCN2 and HCN4 channels, the mode shift effects are not readily observable, except in the tail kinetics. Computer simulations of sino-atrial node action potentials suggest that the HCN2 channel, together with the HCN1 channel, are important regulators of the heart firing frequency and that the mode shift is an important property to prevent arrhythmic firing. We conclude that although all HCN channels appear to undergo mode shifts – and thus may serve to prevent arrhythmic firing – it is mainly observable in ionic currents from HCN channels with faster kinetics. See papers for more and details.
48. Intrinsic sensory neurons of the gut (Chambers et al. 2014)
A conductance base model of intrinsic neurons neurons in the gastrointestinal tract. The model contains all the major voltage-gated and calcium-gated currents observed in these neurons. This model can reproduce physiological observations such as the response to multiple brief depolarizing currents, prolonged depolarizing currents and hyperpolarizing currents. This model can be used to predict how different currents influence the excitability of intrinsic sensory neurons in the gut.
49. Ion channel modeling with whole cell and a genetic algorithm (Gurkiewicz and Korngreen 2007)
"... Here we show that a genetic search algorithm in combination with a gradient descent algorithm can be used to fit whole-cell voltage-clamp data to kinetic models with a high degree of accuracy. Previously, ion channel stimulation traces were analyzed one at a time, the results of these analyses being combined to produce a picture of channel kinetics. Here the entire set of traces from all stimulation protocols are analysed simultaneously. The algorithm was initially tested on simulated current traces produced by several Hodgkin-Huxley–like and Markov chain models of voltage-gated potassium and sodium channels. ... Finally, the algorithm was used for finding the kinetic parameters of several voltage-gated sodium and potassium channels models by matching its results to data recorded from layer 5 pyramidal neurons of the rat cortex in the nucleated outside-out patch configuration. The minimization scheme gives electrophysiologists a tool for reproducing and simulating voltage-gated ion channel kinetics at the cellular level."
50. IP3R model comparison (Hituri and Linne 2013)
In this study, four models of IP3R (Othmer and Tang, 1993; Dawson et al., 2003; Fraiman and Dawson, 2004; Doi et al., 2005) were selected among many to examine their behavior and compare them with experimental data available in literature. The provided MATLAB script (run_IP3R_P0.m) will run the simulations and plot Figure 2A in the paper.
51. Kinetic properties of voltage gated Na channel (Nayak and Sikdar 2007)
Here we illustrate novel non-linear properties of voltage gated Na+ channel induced by sustained membrane depolarization. In cell-attached patch clamp recordings of rNav1.2 channels expressed in CHO cells, we found complex non-linear changes in the molecular kinetic properties, including channel dwell times and unitary conductance of single Na+ channels that were dependent on the extent of conditioning membrane depolarization. A “molecular memory” phenomenon arises at longer depolarization characterized by clusters of dwell time events and strong autocorrelation in dwell times. Hidden Markov Modeling (HMM) ... suggested a possible explanation to the memory phenomenon. See paper for more and details.
52. Kinetics of the P2X7 receptor as expressed in Xenopus oocytes (Riedel et al. 2007a,b)
"Human P2X7 receptors were expressed in Xenopus laevis oocytes and single channels were recorded using the patch-clamp technique in the outside-out configuration. ATP4- evoked two types of P2X7 receptor-mediated single channel currents characterized by short-lived and long-lived openings. ... The kinetics of the short channel openings at negative membrane potentials fitted well to a linear C-C-C-O model with two ATP4- binding steps at equal binding sites ...." and "Using the patch-clamp method, we studied the influence of external alkali and organic monovalent cations on the single-channel properties of the adenosine triphosphate (ATP)-activated recombinant human P2X(7) receptor." See the references for more.
53. KV1 channel governs cerebellar output to thalamus (Ovsepian et al. 2013)
The output of the cerebellum to the motor axis of the central nervous system is orchestrated mainly by synaptic inputs and intrinsic pacemaker activity of deep cerebellar nuclear (DCN) projection neurons. Herein, we demonstrate that the soma of these cells is enriched with KV1 channels produced by mandatory multi-merization of KV1.1, 1.2 alpha andKV beta2 subunits. Being constitutively active, the K+ current (IKV1) mediated by these channels stabilizes the rate and regulates the temporal precision of self-sustained firing of these neurons. ... Through the use of multi-compartmental modelling and ... the physiological significance of the described functions for processing and communication of information from the lateral DCN to thalamic relay nuclei is established.
54. Kv4.3, Kv1.4 encoded K(+) channel in heart cells (Greenstein et al 2000) (XPP)
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:
55. Large scale model of the olfactory bulb (Yu et al., 2013)
The readme file currently contains links to the results for all the 72 odors investigated in the paper, and the movie showing the network activity during learning of odor k3-3 (an aliphatic ketone).
56. Markov models of SCN1A (NaV1.1) applied to abnormal gating and epilepsy (Clancy and Kass 2004)
"Recently, some forms of idiopathic epilepsy have been causally related to genetic mutations in neuronal ion channels. To understand disease mechanisms, it is crucial to understand how a gene defect can disrupt channel gating, which in turn can affect complex cellular dynamic processes. We develop a theoretical Markovian model of the neuronal Na+ channel NaV1.1 to explore and explain gating mechanisms underlying cellular excitability and physiological and pathophysiological mechanisms of abnormal neuronal excitability in the context of epilepsy. ..."
57. Markovian model for cardiac sodium channel (Clancy, Rudy 2002)
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.
58. Markovian model for single-channel recordings of Ik_1 in ventricular cells (Matsuoka et al 2003)
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.
59. Na+ Signals in olfactory bulb neurons (granule cell model) (Ona-Jodar et al. 2017)
Simulations of Na+ during action potentials in granule cells replicated the behaviors observed in experiments.
60. Neocortical Layer I: I-A and I-K (Zhou, Hablitz 1996)
NEURON mod files for the I-A and I-K currents from the paper: Zhou FM, Hablitz JJ. Layer I neurons of the rat neocortex. II. Voltage-dependent outward currents. J Neurophysiol 1996 76:668-82.
61. Neurophysiological impact of inactivation pathways in A-type K+ channels (Fineberg et al 2012)
These models predict the differential effects of varying pathways of inactivation (closed state inactivation, CSI, or open state inactivation, OSI). Specifically, Markov models of Kv4 potassium channels with CSI or CSI+OSI were inserted into the CA1 pyramidal neuron model from Migliore et al (1999; ModelDB accession #2796) to determine the neurophysiological impact of inactivation pathways. Furthermore, Markov models of Kv4.2 and Kv3.4 channels are used to illustrate a method by which to test what pathway of inactivation a channel uses.
62. Nicotinic control of dopamine release in nucleus accumbens (Maex et al. 2014)
Minimal model of the VTA (ventral segmental area) representing two (GABA versus dopamine) neuron populations and two subtypes of nicotinic receptors (alpha4beta2 versus alpha7). The model is used to tell apart circuit from receptor mechanisms in the nicotinic control of dopamine release and its pharmacological manipulation.
63. Novel Na current with slow de-inactivation (Tsutsui, Oka 2002)
The authors found a novel Na current in teleost thalamic nuclei was well described by the m^3 h Hodgkin-Huxley model. The kinetic parameters derived from their experiments (see the reference for details) revealed that the h gate had a large time constant (~100ms at -80 to -50mV). This explains the thalamic neurons long refractory period and the gradual recovery of AP amplitude as the inter spike interval grows.
64. Olfactory Mitral Cell: I-A and I-K currents (Wang et al 1996)
NEURON mod files for the I-A and I-K currents from the paper: X.Y. Wang, J.S. McKenzie and R.E. Kemm, Whole-cell K+ currents in identified olfactory bulb output neurones of rats. J Physiol. 1996 490.1:63-77. Please see the readme.txt included in the model file for more information.
65. Olfactory Periglomerular Cells: I-h kinetics (Cadetti, Belluzzi 2001)
NEURON mod files for the Ih current from the paper: Cadetti L, Belluzzi O. Hyperpolarisation-activated current in glomerular cells of the rat olfactory bulb. Neuroreport 12:3117-20 (2001).
66. On stochastic diff. eq. models for ion channel noise in Hodgkin-Huxley neurons (Goldwyn et al. 2010)
" ... We analyze three SDE models that have been proposed as approximations to the Markov chain model: one that describes the states of the ion channels and two that describe the states of the ion channel subunits. We show that the former channel-based approach can capture the distribution of channel noise and its effect on spiking in a Hodgkin-Huxley neuron model to a degree not previously demonstrated, but the latter two subunit-based approaches cannot. ..."
67. Optical stimulation of a channelrhodopsin-2 positive pyramidal neuron model (Foutz et al 2012)
A computational tool to explore the underlying principles of optogenetic neural stimulation. This "light-neuron" model consists of theoretical representations of the light dynamics generated by a fiber optic in brain tissue, coupled to a multicompartment cable model of a cortical pyramidal neuron (Hu et al. 2009, ModelDB #123897) embedded with channelrhodopsin-2 (ChR2) membrane dynamics. Simulations predict that the activation threshold is sensitive to many of the properties of ChR2 (density, conductivity, and kinetics), tissue medium (scattering and absorbance), and the fiber-optic light source (diameter and numerical aperture). This model system represents a scientific instrument to characterize the effects of optogenetic neuromodulation, as well as an engineering design tool to help guide future development of optogenetic technology.
68. Parametric computation and persistent gamma in a cortical model (Chambers et al. 2012)
Using the Traub et al (2005) model of the cortex we determined how 33 synaptic strength parameters control gamma oscillations. We used fractional factorial design to reduce the number of runs required to 4096. We found an expected multiplicative interaction between parameters.
69. Permeation and inactivation of CaV1.2 Ca2+ channels (Babich et al. 2007)
The authors present data and a kinetics model of the CaV1.2 channel supporting the idea that Ca2+ block of the pore generates the U-shaped inactivation curve.
70. Pipette and membrane patch geometry effects on GABAa currents patch-clamp exps (Moroni et al. 2011)
Ion currents, mediated by GABAa-receptors in outside-out membrane patches, may alter the concentration of Chloride ions inside the pipette and the membrane patch. GABAa-receptors are in fact ionotropic synaptic receptors, selective to Chloride ions. Therefore, chloride fluxes across the membrane patch correlate to GABAa-receptor opening. Chloride ions accumulation, depletion and diffusion, inside the pipette and the membrane patch, affect by definition the Chloride equilibrium (i.e. Nernst) electrical potential. This in turn changes the ionic driving force underlying GABAa-mediated currents. It follows that, in case of very small volumes and confined geometries, voltage-clamp recordings of GABAa-receptor currents carry information on both i) Chloride diffusion and ii) receptor kinetics. The relevance of (i) and (ii) have been studied numerically by defining a 1-dimensional biophysical model, released here to the interested user.
71. Preserving axosomatic spiking features despite diverse dendritic morphology (Hay et al., 2013)
The authors found that linearly scaling the ion channel conductance densities of a reference model with the conductance load in 28 3D reconstructed layer 5 thick-tufted pyramidal cells was necessary to match the experimental statistics of these cells electrical firing properties.
72. Principles of Computational Modelling in Neuroscience (Book) (Sterratt et al. 2011)
"... This book provides a step-by-step account of how to model the neuron and neural circuitry to understand the nervous system at all levels, from ion channels to networks. Starting with a simple model of the neuron as an electrical circuit, gradually more details are added to include the effects of neuronal morphology, synapses, ion channels and intracellular signaling. The principle of abstraction is explained through chapters on simplifying models, and how simplified models can be used in networks. This theme is continued in a final chapter on modeling the development of the nervous system. Requiring an elementary background in neuroscience and some high school mathematics, this textbook is an ideal basis for a course on computational neuroscience."
73. Pyramidal Neuron Deep: K+ kinetics (Korngreen, Sakmann 2000)
NEURON mod files for the slow and fast K+ currents from the paper: Voltage-gated K+ channels in layer 5 neocortical pyramidal neurones from young rats: subtypes and gradients A. Korngreen and B. Sakmann, J.Physiol. 525.3, 621-639 (2000).
74. PyRhO: A multiscale optogenetics simulation platform (Evans et al 2016)
"... we present an integrated suite of open-source, multi-scale computational tools called PyRhO. The purpose of developing PyRhO is three-fold: (i) to characterize new (and existing) opsins by automatically fitting a minimal set of experimental data to three-, four-, or six-state kinetic models, (ii) to simulate these models at the channel, neuron and network levels, and (iii) provide functional insights through model selection and virtual experiments in silico. The module is written in Python with an additional IPython/Jupyter notebook based GUI, allowing models to be fit, simulations to be run and results to be shared through simply interacting with a webpage. The seamless integration of model fitting algorithms with simulation environments (including NEURON and Brian2) for these virtual opsins will enable neuroscientists to gain a comprehensive understanding of their behavior and rapidly identify the most suitable variant for application in a particular biological system. ..."
75. Rat alpha7 nAChR desensitization is modulated by W55 (Gay et al. 2008)
"The rat alpha7 nicotinic acetylcholine receptor (nAChR) can undergo rapid onset of desensitization; however, the mechanisms of desensitization are largely unknown. The contribution of a tryptophan (W) residue at position 55 of the rat alpha7 nAChR subunit, which lies within the beta2 strand, was studied by mutating it to other hydrophobic and/or aromatic amino acids, followed by voltage-clamp experiments in Xenopus oocytes. When mutated to alanine, the alpha7-W55A nAChR desensitized more slowly, and recovered from desensitization more rapidly, than wildtype alpha7 nAChRs. The contribution of desensitization was validated by kinetic modelling. ..."
76. Response of AMPA receptor kinetic model to glutamate release distance (Allam et al., 2015)
These files model the response of an AMPA receptor kinetic model to the release (and diffusion) of glutamate as a function of distance between receptor and release site.
77. Retinal Ganglion Cell: I-A (Benison et al 2001)
NEURON mod files for the K-A current from the papers: (model) Benison G, Keizer J, Chalupa LM, Robinson DW. Modeling temporal behavior of postnatal cat retinal ganglion cells. J.Theor.Biol. 210:187-199 (2001) and (experiment) Skaliora I, Robinson DW, Scobey RP, Chalupa LM., Properties of K+ conductances in cat retinal ganglion cells during the period of activity-mediated refinements in retinofugal pathways. Eur.J.Neurosci. 7:1558-1568 (1995).
78. Retinal Ganglion Cell: I-CaN and I-CaL (Benison et al. 2001)
NEURON mod files for the CaN and CaL currents from the papers: Huang, S.-J. & Robinson, D.W. (1998). Activation and Inactivation properties of voltage-gated calcium currents in developing cat retinal ganglion cells. Neuroscience 85:239-247 (experimental) and Benison G. Keizer J., Chalupa L.M., Robinson D.W., (2001) J. theor. Biol. 210:187-199 (theoretical).
79. Retinal Ganglion Cell: I-K (Skaliora et al 1995)
NEURON mod files for the K-DR current from the paper: Skaliora I, Robinson DW, Scobey RP, Chalupa LM. Properties of K+ conductances in cat retinal ganglion cells during the period of activity-mediated refinements in retinofugal pathways. Eur J Neurosci 1995 7(7):1558-1568. See the readme.txt file below for more information.
80. Retinal Ganglion Cell: I-Na,t (Benison et al 2001)
NEURON mod files for the Na current from the papers: (model) Benison G, Keizer J, Chalupa LM, Robinson DW. Modeling temporal behavior of postnatal cat retinal ganglion cells. J Theor Biol. 2001 210:187-99 and a reference from this paper: (experimental) Skaliora I, Scobey RP, Chalupa LM. Prenatal development of excitability in cat retinal ganglion cells: action potentials and sodium currents. J Neurosci 1993 13:313-23. See the readme.txt file below for more information.
81. Retinal Photoreceptor: I Potassium (Beech, Barnes 1989)
NEURON mod files for a Potassium current from the paper: Beech DJ, Barnes S. Characterization of a voltage-gated K+ channel that accelerates the rod response to dim light. Neuron 3:573-81 (1989).
82. Role of KCNQ1 and IKs in cardiac repolarization (Silva, Rudy 2005)
Detailed Markov models of IKs (the slow delayed rectifier K+ current) and its alpha-subunit KCNQ1 were developed. 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 paper for more and details.
83. Role of KCNQ1 and IKs in cardiac repolarization (Silva, Rudy 2005) (XPP)
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
84. Simulating ion channel noise in an auditory brainstem neuron model (Schmerl & McDonnell 2013)
" ... Here we demonstrate that biophysical models of channel noise can give rise to two kinds of recently discovered stochastic facilitation effects in a Hodgkin-Huxley-like model of auditory brainstem neurons. The first, known as slope-based stochastic resonance (SBSR), enables phasic neurons to emit action potentials that can encode the slope of inputs that vary slowly relative to key time constants in the model. The second, known as inverse stochastic resonance (ISR), occurs in tonically firing neurons when small levels of noise inhibit tonic firing and replace it with burstlike dynamics. ..." Preprint available at
85. Sodium currents activate without a delay (Baranauskas and Martina 2006)
Hodgkin and Huxley established that sodium currents in the squid giant axons activate after a delay, which is explained by the model of a channel with three identical independent gates that all have to open before the channel can pass current (the HH model). It is assumed that this model can adequately describe the sodium current activation time course in all mammalian central neurons, although there is no experimental evidence to support such a conjecture. We performed high temporal resolution studies of sodium currents gating in three types of central neurons. ... These results can be explained by a model with two closed states and one open state. ... This model captures all major properties of the sodium current activation. In addition, the proposed model reproduces the observed action potential shape more accurately than the traditional HH model. See paper for more and details.
86. Specific inhibition of dendritic plateau potential in striatal projection neurons (Du et al 2017)
We explored dendritic plateau potentials in a biophysically detailed SPN model. We coupled the dendritic plateaus to different types of inhibitions (dendritic fast and slow inhibitions, perisomatic inhibition from FS interneurons , etc.) We found the inhibition provides precise control over the plateau potential, and thus the spiking output of SPNs.
87. Spike propagation in dendrites with stochastic ion channels (Diba et al. 2006)
"We investigate the effects of the stochastic nature of ion channels on the faithfulness, precision and reproducibility of electrical signal transmission in weakly active, dendritic membrane under in vitro conditions. ... We numerically simulate the effects of stochastic ion channels on the forward and backward propagation of dendritic spikes in Monte-Carlo simulations on a reconstructed layer 5 pyramidal neuron. We report that in most instances there is little variation in timing or amplitude for a single BPAP, while variable backpropagation can occur for trains of action potentials. Additionally, we find that the generation and forward propagation of dendritic Ca2+ spikes are susceptible to channel variability. This indicates limitations on computations that depend on the precise timing of Ca2+ spikes."
88. Spinal Motor Neuron: Na, K_A, and K_DR currents (Safronov, Vogel 1995)
NEURON mod files for the Na, K-A, and K-DR currents from the paper: Safronov, B.V. and Vogel,W. Single voltage-activated Na+ and K+ channels in the somata of rat motorneurons. Journal of Physiology 487.1:91-106 (1995). See the readme.txt file for more information.
89. Spontaneous firing caused by stochastic channel gating (Chow, White 1996)
NEURON implementation of model of stochastic channel gating, resulting in spontaneous firing. Qualitatively reproduces the phenomena described in the reference.
90. State dependent drug binding to sodium channels in the dentate gyrus (Thomas & Petrou 2013)
A Markov model of sodium channels was developed that includes drug binding to fast inactivated states. This was incorporated into a model of the dentate gyrus to investigate the effects of anti-epileptic drugs on neuron and network properties.
91. Stochastic automata network Markov model descriptors of coupled Ca2+ channels (Nguyen et al. 2005)
"... Here we present a formalism by which mathematical models for Ca2+-regulated Ca2+ release sites are derived from stochastic models of single-channel gating that include Ca2+ activation, Ca2+ inactivation, or both. Such models are stochastic automata networks (SANs) that involve a large number of functional transitions, that is, the transition probabilities of the infinitesimal generator matrix of one of the automata (i.e., an individual channel) may depend on the local [Ca2+] and thus the state of the other channels. Simulation and analysis of the SAN descriptors representing homogeneous clusters of intracellular Ca2+ channels show that (1) release site density can modify both the steady-state open probability and stochastic excitability of Ca2+ release sites, (2) Ca2+ inactivation is not a requirement for Ca2+ puffs or sparks, and (3) a single-channel model with a bell-shaped open probability curve does not lead to release site activity that is a biphasic function of release site density. ..."
92. Stochastic ion channels and neuronal morphology (Cannon et al. 2010)
"... We introduce and validate new computational tools that enable efficient generation and simulation of models containing stochastic ion channels distributed across dendritic and axonal membranes. Comparison of five morphologically distinct neuronal cell types reveals that when all simulated neurons contain identical densities of stochastic ion channels, the amplitude of stochastic membrane potential fluctuations differs between cell types and depends on sub-cellular location. ..." The code is downloadable and more information is available at <a href=""></a>
93. Stochastic model of the olfactory cilium transduction and adaptation (Antunes et al 2014)
" ... In this work, we have combined stochastic computational modeling and a systematic pharmacological study of different signaling pathways to investigate their impact during short-term adaptation (STA). ... These results suggest that G-coupled receptors (GPCRs) cycling is involved with the occurrence of STA. To gain insights on the dynamical aspects of this process, we developed a stochastic computational model. The model consists of the olfactory transduction currents mediated by the cyclic nucleotide gated (CNG) channels and calcium ion (Ca2+)-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca2+, and it simulates the EOG (electroolfactogram) results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca2+ response, two second messengers implicated with STA occurrence. The model reproduced the experimental data for each pharmacological treatment and provided a mechanistic explanation for the action of GPCR cycling in the levels of second messengers modulating the levels of STA. All together, these experimental and theoretical results indicate the existence of a mechanism of regulation of STA by signaling pathways that control GPCR cycling and tune the levels of second messengers in OSNs, and not only by CNG channel desensitization as previously thought. "
94. Subthreshold inact. of K channels modulates APs in bitufted interneurons (Korngreen et al 2005)
... In this study we show that in bitufted interneurones from layer 2/3 of the somatosensory cortex, the height and width of APs recorded at the soma are sensitive to changes in the resting membrane potential, suggesting subthreshold activity of voltage-gated conductances. Attributes of K+ currents examined in nucleated patches revealed a fast subthreshold-inactivating K+ conductance (Kf ) and a slow suprathreshold-inactivating K+ conductance (Ks ). Simulations of these K+ conductances, incorporated into a Hodgkin–Huxley-type model, suggested that during a single AP or during low frequency trains of APs, subthreshold inactivation of Kf was the primary modulator of AP shape, whereas during trains of APs the shape was governed to a larger degree by Ks resulting in the generation of smaller and broader APs. ... Compartmental simulation of the back-propagating AP suggested a mechanism for the modulation of the back-propagating AP height and width by subthreshold activation of Kf . We speculate that this signal may modulate retrograde GABA release and consequently depression of synaptic ef&#64257;cacy of excitatory input from neighbouring pyramidal neurones.
95. Synergistic inhibitory action of oxcarbazepine on INa and IK (Huang et al. 2008)
"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."
96. T channel currents (Vitko et al 2005)
Computer simulations predict that seven of the SNPs would increase firing of neurons, with three of them inducing oscillations at similar frequencises. 3 representative models from the paper have been submited: a wild-type (WT) recombinant Cav3.2 T-channel, and two of the mutants described in the Vitko et al., 2005 paper (C456S and R788C). See the paper for more and details.
97. T-type Calcium currents (McRory et al 2001)
NEURON mod files for CaT currents from the paper McRory et al., J.Biol.Chem. 276:3999 (2001). In this paper, three members (alpha-1G, -1H, and -1I) of the LVA calcium channels family were studied. Kinetic parameters were derived from functional expression in transfected cells.
98. Thalamic Relay Neuron: I-h (McCormick, Pape 1990)
NEURON mod files for the Ih current from the paper: McCormick DA, Pape HC. Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurones. J. Physiol. 1990 431:291-318.
99. Thalamic Relay Neuron: I-T current (Williams, Stuart 2000)
NEURON mod files for the Ca-T current from the paper: Williams SR, Stuart GJ, Action potential backpropagation and somato-dendritic distribution of ion channels in thalamocortical neurons. J Neurosci. 2000 20:1307-17. Contact if you have any questions about the implementation of the model.

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