Models that contain the Model Concept : Axonal Action Potentials

(The model is used to investigate action potential propagation in axons.)
Re-display model names without descriptions
    Models   Description
1.  A detailed Purkinje cell model (Masoli et al 2015)
The Purkinje cell is one of the most complex type of neuron in the central nervous system and is well known for its massive dendritic tree. The initiation of the action potential was theorized to be due to the high calcium channels presence in the dendritic tree but, in the last years, this idea was revised. In fact, the Axon Initial Segment, the first section of the axon was seen to be critical for the spontaneous generation of action potentials. The model reproduces the behaviours linked to the presence of this fundamental sections and the interplay with the other parts of the neuron.
2.  A model for interaural time difference sensitivity in the medial superior olive (Zhou et al 2005)
This model simulates responses of neurons to interaural time difference (ITD) in the medial superior olive (MSO) of the mammalian brainstem. The model has a bipolar cell structure and incorporates two anatomic observations in the MSO: (1) the axon arises from the dendrite that receives ipsilateral inputs and (2) inhibitory synapses are located primarily on the soma in adult animals. Fine adjustment of the best ITD is achieved by the interplay of somatic sodium currents and synaptic inhibitory currents. The model suggests a mechanism for dynamically "fine-tuning" the ITD sensitivity of MSO cells by the opponency between depolarizing sodium currents and hyperpolarizing inhibitory currents.
3.  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."
4.  CA1 pyramidal cell: reconstructed axonal arbor and failures at weak gap junctions (Vladimirov 2011)
Model of pyramidal CA1 cells connected by gap junctions in their axons. Cell geometry is based on anatomical reconstruction of rat CA1 cell (NeuroMorpho.Org ID: NMO_00927) with long axonal arbor. Model init_2cells.hoc shows failures of second spike propagation in a spike doublet, depending on conductance of an axonal gap junction. Model init_ring.hoc shows that spike failure result in reentrant oscillations of a spike in a loop of axons connected by gap junctions, where one gap junction is weak. The paper shows that in random networks of axons connected by gap junctions, oscillations are driven by single pacemaker loop of axons. The shortest loop, around which a spike can travel, is the most likely pacemaker. This principle allows us to predict the frequency of oscillations from network connectivity and visa versa. We propose that this type of oscillations corresponds to so-called fast ripples in epileptic hippocampus.
5.  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.
6.  Conduction in uniform myelinated axons (Moore et al 1978)
Examines the relative sensitivity of the velocity of impulse propagation to changes in nodal and internodal parameters.
7.  Contribution of the axon initial segment to APs recorded extracellularly (Telenczuk et al 2018)
"... It was recently proposed that at onset of an (Action Potential) AP the soma and the (Axon Initial Segment) AIS form a dipole. We study the extracellular signature (the extracellular action potential, EAP) generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. ..."
8.  Current flow during PAP in squid axon at diameter change (Joyner et al 1980)
From the paper abstract: An impulse ... sees an increased electrical load at regions of increasing diameter or at branch points with certain morphologies. We present here theoretical and experimental studies on the changes in membrane current and axial current associated with diameter changes. The theoretical studies were done with numerical solutions for cable equations that were generalized to include a varying diameter; the Hodgkin-Huxley equations were used to represent the membrane properties. ... As an action potential approaches a region of increased electrical load, the action potential amplitude and rate of rise decrease, but there is a marked increase in the magnitude of the inward sodium current. ... (See paper for more details.)
9.  Demyelinated and remyelinating axon conductances (Hines, Shrager 1991)
Hines, Michael and Peter Shrager (1991). A computational test of the requirements for conduction in demyelinated axons. J. Restorative Neurology and Neuroscience. 3 81--93.
10.  Dendritica (Vetter et al 2001)
Dendritica is a collection of programs for relating dendritic geometry and signal propagation. The programs are based on those used for the simulations described in: Vetter, P., Roth, A. & Hausser, M. (2001) For reprint requests and additional information please contact Dr. M. Hausser, email address: m.hausser@ucl.ac.uk
11.  Dentate gyrus network model (Santhakumar et al 2005)
Mossy cell loss and mossy fiber sprouting are two characteristic consequences of repeated seizures and head trauma. However, their precise contributions to the hyperexcitable state are not well understood. Because it is difficult, and frequently impossible, to independently examine using experimental techniques whether it is the loss of mossy cells or the sprouting of mossy fibers that leads to dentate hyperexcitability, we built a biophysically realistic and anatomically representative computational model of the dentate gyrus to examine this question. The 527-cell model, containing granule, mossy, basket, and hilar cells with axonal projections to the perforant-path termination zone, showed that even weak mossy fiber sprouting (10-15% of the strong sprouting observed in the pilocarpine model of epilepsy) resulted in the spread of seizure-like activity to the adjacent model hippocampal laminae after focal stimulation of the perforant path. See reference for more and details.
12.  Dorsal root ganglion (DRG) neuronal model (Amir, Devor 2003)
The model shows that an electrically excitable soma is not necessary for spike through-conduction in the t-shaped geometry of a dorsal root ganglion neuron axon. Electrical excitability of the soma is required, however, for soma spike invasion. See papers for details and more.
13.  Effects of Acetyl-L-carnitine on neural transmission (Lombardo et al 2004)
Acetyl-L-carnitine is known to improve many aspects of the neural activity even if its exact role in neurotransmission is still unknown. This study investigates the effects of acetyl-L-carnitine in T segmental sensory neurons of the leech Hirudo medicinalis. These neurons are involved in some forms of neural plasticity associated with learning processes. Their physiological firing is accompanied by a large afterhyperpolarization that is mainly due to the Na+/K+ ATPase activity and partially to a Ca2+-dependent K+ current. A clear-cut hyperpolarization and a significant increase of the afterhyperpolarization have been recorded in T neurons of leeches injected with 2 mM acetyl-L-carnitine some days before. Acute treatments of 50 mM acetyl-L-carnitine induced similar effects in T cells of naive animals. Moreover, in these cells, widely arborized, the afterhyperpolarization seems to play an important role in determining the action potential transmission at neuritic bifurcations. A computational model of a T cell has been previously developed considering detailed data for geometry and the modulation of the pump current. Herein, we showed that to a larger afterhyperpolarization, due to the acetyl-L-carnitine-induced effects, corresponds a decrement in the number of action potentials reaching synaptic terminals.
14.  Ephaptic interactions in olfactory nerve (Bokil et al 2001)
Bokil, H., Laaris, N., Blinder, K., Ennis, M., and Keller, A. (2001) Ephaptic interactions in the mammalian olfactory system. J. Neurosci. 21:RC173(1-5)
15.  GPi/GPe neuron models (Johnson and McIntyre 2008)
Model files for two types of non-human primate neurons used in the paper: simplified versions of 1) a GPi neuron and 2) a GPe axon collateralizing in GPi en route to STN.
16.  High frequency oscillations induced in three gap-junction coupled neurons (Tseng et al. 2008)
Here we showed experimentally that high frequency oscillations (up to 600 Hz) were easily induced in a purely gap-junction coupled network by simple two stimuli with very short interval. The root cause is that the second elicited spike suffered from slow propagation speed and failure to transmit through a low-conductance junction. Similiar results were also obtained in these simulation.
17.  Leech Mechanosensory Neurons: Synaptic Facilitation by Reflected APs (Baccus 1998)
This model by Stephen Baccus explores the phenomena of action potential (AP) propagation at branch boints in axons. APs are sometimes transmitted down the efferent processes and sometimes are reflected back to the axon of AP origin or neither. See the paper for details. The model zip file contains a readme.txt which list introductory steps to follow to run the simulation. Stephen Baccus's email address: baccus@fas.harvard.edu
18.  MCCAIS model (multicompartmental cooperative AIS) (Öz et al 2015)
Action potential initiation in a multi-compartmental model with cooperatively gating Na channels in the axon initial segment.
19.  Mechanisms of fast rhythmic bursting in a layer 2/3 cortical neuron (Traub et al 2003)
This simulation is based on the reference paper listed below. This port was made by Roger D Traub and Maciej T Lazarewicz (mlazarew at seas.upenn.edu) Thanks to Ashlen P Reid for help with porting a morphology of the cell.
20.  Mechanisms of very fast oscillations in axon networks coupled by gap junctions (Munro, Borgers 2010)
Axons connected by gap junctions can produce very fast oscillations (VFOs, > 80 Hz) when stimulated randomly at a low rate. The models here explore the mechanisms of VFOs that can be seen in an axonal plexus, (Munro & Borgers, 2009): a large network model of an axonal plexus, small network models of axons connected by gap junctions, and an implementation of the model underlying figure 12 in Traub et al. (1999) . The large network model consists of 3,072 5-compartment axons connected in a random network. The 5-compartment axons are the 5 axonal compartments from the CA3 pyramidal cell model in Traub et al. (1994) with a fixed somatic voltage. The random network has the same parameters as the random network in Traub et al. (1999), and axons are stimulated randomly via a Poisson process with a rate of 2/s/axon. The small network models simulate waves propagating through small networks of axons connected by gap junctions to study how local connectivity affects the refractory period.
21.  Multicompartmental cerebellar granule cell model (Diwakar et al. 2009)
A detailed multicompartmental model was used to study neuronal electroresponsiveness of cerebellar granule cells in rats. Here we show that, in cerebellar granule cells, Na+ channels are enriched in the axon, especially in the hillock, but almost absent from soma and dendrites. Numerical simulations indicated that granule cells have a compact electrotonic structure allowing EPSPs to diffuse with little attenuation from dendrites to axon. The spike arose almost simultaneously along the whole axonal ascending branch and invaded the hillock, whose activation promoted spike back-propagation with marginal delay (<200 micros) and attenuation (<20 mV) into the somato-dendritic compartment. For details check the cited article.
22.  Multiscale model of olfactory receptor neuron in mouse (Dougherty 2009)
Collection of XPP (.ode) files simulating the signal transduction (slow) and action potential (fast) currents in the olfactory receptor neuron of mouse. Collection contains model configured for dual odorant pulse delivery and model configured for prolonged odorant delivery. For those interested more in transduction processes, each whole cell recording model comes with a counter part file configured to show just the slow transduction current for ease of use and convenience. These transduction-only models typically run faster than the full multi-scale models but do not demonstrate action potentials.
23.  Myelinated axon conduction velocity (Brill et al 1977)
Examines conduction velocity as function of internodal length.
24.  Na+ channel dependence of AP initiation in cortical pyramidal neuron (Kole et al. 2008)
In this simulation action potential initiation, action potential properties and the role of axon initial segment Na+ channels are investigated in a realistic model of a layer 5 pyramidal neuron axon initial segment. The main Na+ channel properties were constrained by experimental data and the axon initial segment was reconstructed. Model parameters were constrained by direct recordings at the axon initial segment.
25.  Neocort. pyramidal cells subthreshold somatic voltage controls spike propagation (Munro Kopell 2012)
There is suggestive evidence that pyramidal cell axons in neocortex may be coupled by gap junctions into an ``axonal plexus" capable of generating Very Fast Oscillations (VFOs) with frequencies exceeding 80 Hz. It is not obvious, however, how a pyramidal cell in such a network could control its output when action potentials are free to propagate from the axons of other pyramidal cells into its own axon. We address this problem by means of simulations based on 3D reconstructions of pyramidal cells from rat somatosensory cortex. We show that somatic depolarization enables propagation via gap junctions into the initial segment and main axon, while somatic hyperpolarization disables it. We show further that somatic voltage cannot effectively control action potential propagation through gap junctions on minor collaterals; action potentials may therefore propagate freely from such collaterals regardless of somatic voltage. In previous work, VFOs are all but abolished during the hyperpolarization phase of slow-oscillations induced by anesthesia in vivo. This finding constrains the density of gap junctions on collaterals in our model and suggests that axonal sprouting due to cortical lesions may result in abnormally high gap junction density on collaterals, leading in turn to excessive VFO activity and hence to epilepsy via kindling.
26.  Neurite: electrophysiological-mechanical coupling simulation framework (Garcia-Grajales et al 2015)
Neurite simulates the electrical signal propagation in myelinated and unmyelinated axons, and in dendritic trees under mechanical loading. Two different solvers are available (explicit and implicit) with sequential (CPU) and parallel (GPUs) versions
27.  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.
28.  Prediction for the presence of voltage-gated Ca2+ channels in myelinated central axons (Brown 2003)
"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."
29.  Regulation of motoneuron excitability by KCNQ/Kv7 modulators (Lombardo & Harrington 2016)
" ... Computer simulations confirmed that pharmacological enhancement of KCNQ/Kv7 channel (M current) activity decreases excitability and also suggested that the effects of inhibition of KCNQ/Kv7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/Kv7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. ..."
30.  Salamander retinal ganglian cells: morphology influences firing (Sheasby, Fohlmeister 1999)
Nerve impulse entrainment and other excitation and passive phenomena are analyzed for a morphologically diverse and exhaustive data set (n=57) of realistic (3-dimensional computer traced) soma-dendritic tree structures of ganglion cells in the tiger salamander (Ambystoma tigrinum) retina.
31.  Sharpness of spike initiation in neurons explained by compartmentalization (Brette 2013)
"Spike initiation determines how the combined inputs to a neuron are converted to an output. Since the pioneering work of Hodgkin and Huxley, it is known that spikes are generated by the opening of sodium channels with depolarization. According to this standard theory, these channels should open gradually when the membrane potential increases, but spikes measured at the soma appear to suddenly rise from rest. This apparent contradiction has triggered a controversy about the origin of spike “sharpness.” This study shows with biophysical modelling that if sodium channels are placed in the axon rather than in the soma, they open all at once when the somatic membrane potential exceeds a critical value. This work explains the sharpness of spike initiation and provides another demonstration that morphology plays a critical role in neural function."
32.  Spike Initiation in Neocortical Pyramidal Neurons (Mainen et al 1995)
This model reproduces figure 3A from the paper Mainen ZF, Joerges J, Huguenard JR, Sejnowski TJ (1995). Please see the paper for detail whose full text is available at http://www.cnl.salk.edu/~zach/methods.html Email Zach Mainen for questions: mainen@cshl.org
33.  Spike propagation and bouton activation in terminal arborizations (Luscher, Shiner 1990)
Action potential propagation in axons with bifurcations involving short collaterals with synaptic boutons has been simulated ... The architecture of the terminal arborizations has a profound effect on the activation pattern of synapses, suggesting that terminal arborizations not only distribute neural information to postsynaptic cells but may also be able to process neural information presynaptically. Please see paper for details.
34.  Spike trains in Hodgkin–Huxley model and ISIs of acupuncture manipulations (Wang et al. 2008)
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.
35.  Spikelet generation and AP initiation in a L5 neocortical pyr neuron (Michalikova et al. 2017) Fig 1
The article by Michalikova et al. (2017) explores the generation of spikelets in cortical pyramidal neurons. The model cell, adapted from Hu et al. (2009), is a layer V pyramidal neuron. The cell is stimulated by fluctuating synaptic inputs and generates somatic APs and spikelets in response. The spikelets are initiated as APs at the AIS that do not activate the soma.
36.  Spikelet generation and AP initiation in a simplified pyr neuron (Michalikova et al. 2017) Fig 3
The article by Michalikova et al. (2017) explores the generation of spikelets in cortical pyramidal neurons. This package contains code for simulating the model with simplified morphology shown in Figs 3 and S2.
37.  Spinal Motor Neuron (Dodge, Cooley 1973)
"The excitability of various regions of the spinal motorneuron can be specified by solving the partial differential equation of a nerve fiber whose diameter and membrane properties vary with distance. For our model geometrical factors for the myelinated axon, initial segment and cell body were derived from anatomical measurements, the dendritic tree was represented by its equivalent cylinder, and the current-voltage relations of the membrane were described by a modification of the Hodgkin-Huxley model that fits voltage-clamp data from the motorneuron. ..."
38.  Spinal Motor Neuron (McIntyre et al 2002)
Simulation of peripheral nervous system (PNS) mylelinated axon. This model is described in detail in: McIntyre CC, Richardson AG, and Grill WM.(2002)
39.  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.
40.  Stimulated and physiologically induced APs: frequency and fiber diameter (Sadashivaiah et al 2018)
"... In this study, we aim to quantify the effects of stimulation frequency and fiber diameter on AP (Action Potential) interactions involving collisions and loss of excitability. We constructed a mechanistic model of a myelinated nerve fiber receiving two inputs: the underlying physiological activity at the terminal end of the fiber, and an external stimulus applied to the middle of the fiber. We define conduction reliability as the percentage of physiological APs that make it to the somatic end of the nerve fiber. At low input frequencies, conduction reliability is greater than 95% and decreases with increasing frequency due to an increase in AP interactions. Conduction reliability is less sensitive to fiber diameter and only decreases slightly with increasing fiber diameter. Finally, both the number and type of AP interactions significantly vary with both input frequencies and fiber diameter. ..."
41.  Submyelin Potassium accumulation in Subthalamic neuron (STN) axons (Bellinger et al. 2008)
"To better understand the direct effects of DBS (Deep brain stimulation) on central neurons, a computational model of a myelinated axon has been constructed which includes the effects of K+ accumulation within the peri-axonal space. Using best estimates of anatomic and electrogenic model parameters for in vivo STN axons, the model predicts a functional block along the axon due to K+ accumulation in the submyelin space. ... These results suggest that therapeutic DBS of the STN likely results in a functional block for many STN axons, although a subset of STN axons may also be activated at the stimulating frequency. "
42.  Synaptic gating at axonal branches, and sharp-wave ripples with replay (Vladimirov et al. 2013)
The computational model of in vivo sharp-wave ripples with place cell replay. Excitatory post-synaptic potentials at dendrites gate antidromic spikes arriving from the axonal collateral, and thus determine when the soma and the main axon fire. The model allows synchronous replay of pyramidal cells during sharp-wave ripple event, and the replay is possible in both forward and reverse directions.
43.  Temperature-Sensitive conduction at axon branch points (Westerfield et al 1978)
Propagation of impulses through branching regions of squid axons was examined experimentally and with computer simulations. The ratio of postbranch/prebranch diameters at which propagation failed was very sensitive to temperature.
44.  Thalamic network model of deep brain stimulation in essential tremor (Birdno et al. 2012)
"... Thus the decreased effectiveness of temporally irregular DBS trains is due to long pauses in the stimulus trains, not the degree of temporal irregularity alone. We also conducted computer simulations of neuronal responses to the experimental stimulus trains using a biophysical model of the thalamic network. Trains that suppressed tremor in volunteers also suppressed fluctuations in thalamic transmembrane potential at the frequency associated with cerebellar burst-driver inputs. Clinical and computational findings indicate that DBS suppresses tremor by masking burst-driver inputs to the thalamus and that pauses in stimulation prevent such masking. Although stimulation of other anatomic targets may provide tremor suppression, we propose that the most relevant neuronal targets for effective tremor suppression are the afferent cerebellar fibers that terminate in the thalamus."
45.  The basis of sharp spike onset in standard biophysical models (Telenczuk et al 2017)
"In most vertebrate neurons, spikes initiate in the axonal initial segment (AIS). When recorded in the soma, they have a surprisingly sharp onset, as if sodium (Na) channels opened abruptly. The main view stipulates that spikes initiate in a conventional manner at the distal end of the AIS, then progressively sharpen as they backpropagate to the soma. We examined the biophysical models used to substantiate this view, and we found that spikes do not initiate through a local axonal current loop that propagates along the axon, but through a global current loop encompassing the AIS and soma, which forms an electrical dipole. Therefore, the phenomenon is not adequately modeled as the backpropagation of an electrical wave along the axon, since the wavelength would be as large as the entire system. Instead, in these models, we found that spike initiation rather follows the critical resistive coupling model proposed recently, where the Na current entering the AIS is matched by the axial resistive current flowing to the soma. ..."
46.  Tight junction model of CNS myelinated axons (Devaux and Gow 2008)
Two models are included: 1) a myelinated axon is represented by an equivalent circuit with a double cable design but includes a tight junction in parallel with the myelin membrane RC circuit (called double cable model, DCM). 2) a myelinated axon is represented by an equivalent circuit with a double cable design but includes a tight junction in series with the myelin RC circuit (called tight junction model, TJM). These models have been used to simulate data from compound action potentials measured in mouse optic nerve from Claudin 11-null mice in Fig. 6 of: Devaux, J.J. & Gow, A. (2008) Tight Junctions Potentiate The Insulative Properties Of Small CNS Myelinated Axons. J Cell Biol 183, 909-921.
47.  Touch Sensory Cells (T Cells) of the Leech (Cataldo et al. 2004) (Scuri et al. 2007)
Bursts of spikes in leech T cells produce an AHP, which results from activation of a Na+/K+ pump and a Ca2+-dependent K+ current. Activity-dependent increases in the AHP are believed to induce conduction block of spikes in several regions of the neuron, which in turn, may decrease presynaptic invasion of spikes and thereby decrease transmitter release. To explore this possibility, we used the neurosimulator SNNAP to develop a multi-compartmental model of the T cell. Each compartment was modeled as an equivalent electrical circuit, in which some currents were regulated by intracellular Ca2+ and Na+. The membrane model consisted of a membrane capacitance (Cm), for which we used the value 1 uF/cm2, in parallel with two inward currents (Na+ and Ca2+), two K+ currents, a leak current and pump current. The model incorporated empirical data that describe the geometry of the cell and activity-dependent changes of the AHP (see paper for details). Simulations indicated that at some branching points, activity-dependent increases of the AHP reduced the number of spikes transmitted from the minor receptive field to the soma and beyond. These results suggest that the AHP can regulate spike conduction within the presynaptic arborizations of the cell and could in principle contribute to the synaptic depression that is correlated with increases in the AHP.
48.  Xenopus Myelinated Neuron (Frankenhaeuser, Huxley 1964)
Frankenhaeuser, B. and Huxley, A. F. (1964), The action potential in the myelinated nerve fiber of Xenopus Laevis as computed on the basis of voltage clamp data. J. Physiol. 171: 302-315. See README file for more information.
49.  Zonisamide-induced inhibition of the firing of APs in hippocampal neurons (Huang et al. 2007)
Zonisamide (ZNS), a synthetic benzisoxazole derivative, has been used as an alternative choice in the treatment of epilepsy with a better efficacy and safety profile. However, little is known regarding the mechanism of ZNS actions on ion currents in neurons. We thus investigated its effect on ion currents in differentiated hippocampal 19-7 cells. The ZNS (30 uM) reversibly increased the amplitude of K+ outward currents and paxilline (1 uM) was effective in suppressing ZNS-induced increase of K+ outward currents. In inside-out configuration, ZNS (30 uM) applied to the intracellular face of the membrane did not alter single-channel conductance; however, it did enhance the activity of large-conductance Ca2+-activated K+ (BKCa) channels primarily by decreasing mean closed time. The EC50 value for ZNS-stimulated BKCa channels was 34 uM. This drug caused a left shift in the activation curve of BKCa channels with no change in the gating charge of these channels. ZNS at a concentration greater than 100 uM also reduced the amplitude of A-type K+ current in these cells. A simulation modeling based on hippocampal CA3 pyramidal neurons (Pinsky-Rinzel model) was also analyzed to investigate the inhibitory effect of ZNS on the firing of simulated action potentials. Taken together, this study suggests that in hippocampal neurons, during the exposure to ZNS, the ZNS-mediated effects on BKCa channels and IA could be one of the ionic mechanisms through which it affects neuronal excitability.

Re-display model names without descriptions