|
|
| Models | Description |
| A dynamic model of the canine ventricular myocyte (Hund, Rudy 2004) | |
| The Hund-Rudy dynamic (HRd) model is based on data from the canine epicardial ventricular myocyte. Rate-dependent phenomena associated with ion channel kinetics, action potential properties and Ca2+ handling are simulated by the model. See paper for more and details. | |
| A multiphysics neuron model for cellular volume dynamics (Lee et al. 2011) | |
| This paper introduces a novel neuron model, where the cell volume is a time-varying variable and multiple physical principles are combined to build governing equations. Using this model, we analyzed neuronal volume responses during excitation, which elucidated the waveforms of fast intrinsic optical signals observed experimentally across the literature. In addition, we analyzed volume responses on a longer time scale with repetitive stimulation to study the characteristics of slow cell swelling. | |
| Alcohol excites Cerebellar Golgi Cells by inhibiting the Na+/K+ ATPase (Botta et al.2010) | |
| Patch-clamp in cerebellar slices and computer modeling show that ethanol excites Golgi cells by inhibiting the Na+/K+ ATPase. In particular, voltage-clamp recordings of Na+/K+ ATPase currents indicated that ethanol partially inhibits this pump and this effect could be mimicked by low concentrations of the Na+/K+ ATPase blocker ouabain. The partial inhibition of Na+/K+ ATPase in a computer model of the Golgi cell reproduced these experimental findings that established a novel mechanism of action of ethanol on neural excitability. | |
| Biophysically detailed model of the mouse sino-atrial node cell (Kharche et al. 2011) | |
| This model is developed to study the role of various electrophysiological mechanisms in generating cardiac pacemaking action potentials (APs).The model incorporates membrane ionic currents and intracellular mechanisms contributing to spontaneous mouse SAN APs. The model was validated by testing the functional roles of individual membrane currents in one and multiple parameter analyses.The roles of intracellular Ca2+-handling mechanisms on cardiac pacemaking were also investigated in the model. | |
| Cardiac Atrial Cell (Courtemanche et al 1998) (C++) | |
| The mechanisms underlying many important properties of the human atrial action potential (AP) are poorly understood. Using specific formulations of the K+, Na+, and Ca2+ currents based on data recorded from human atrial myocytes, along with representations of pump, exchange, and background currents, we developed a mathematical model of the AP. The model AP resembles APs recorded from human atrial samples and responds to rate changes, L-type Ca2+ current blockade, Na+/Ca2+ exchanger inhibition, and variations in transient outward current amplitude in a fashion similar to experimental recordings. Rate-dependent adaptation of AP duration, an important determinant of susceptibility to atrial fibrillation, was attributable to incomplete L-type Ca2+ current recovery from inactivation and incomplete delayed rectifier current deactivation at rapid rates. Experimental observations of variable AP morphology could be accounted for by changes in transient outward current density, as suggested experimentally. We conclude that this mathematical model of the human atrial AP reproduces a variety of observed AP behaviors and provides insights into the mechanisms of clinically important AP properties. | |
| Cardiac action potentials and pacemaker activity of sinoatrial node (DiFrancesco & Noble 1985) | |
| "Equations have been developed to describe cardiac action potentials and pacemaker activity. The model takes account of extensive developments in experimental work ..." | |
| Computer simulations of neuron-glia interactions mediated by ion flux (Somjen et al. 2008) | |
| "... To examine the effect of glial K+ uptake, we used a model neuron equipped with Na+, K+, Ca2+ and Cl− conductances, ion pumps and ion exchangers, surrounded by interstitial space and glia. The glial membrane was either “passive”, incorporating only leak channels and an ion exchange pump, or it had rectifying K+ channels. We computed ion fluxes, concentration changes and osmotic volume changes. ... We conclude that voltage gated K+ currents can boost the effectiveness of the glial “potassium buffer” and that this buffer function is important even at moderate or low levels of excitation, but especially so in pathological states." | |
| Differential modulation of pattern and rate in a dopamine neuron model (Canavier and Landry 2006) | |
| "A stylized, symmetric, compartmental model of a dopamine neuron in vivo shows how rate and pattern can be modulated either concurrently or differentially. If two or more parameters in the model are varied concurrently, the baseline firing rate and the extent of bursting become decorrelated, which provides an explanation for the lack of a tight correlation in vivo and is consistent with some independence of the mechanisms that generate baseline firing rates versus bursting. ..." See paper for more and details. | |
| 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. | |
| INa and IKv4.3 heterogeneity in canine LV myocytes (Flaim et al 2006) | |
| "The roles of sustained components of INa and IKv43 in shaping the action potentials (AP) of myocytes isolated from the canine left ventricle (LV) have not been studied in detail. Here we investigate the hypothesis that these two currents can contribute substantially to heterogeneity of early repolarization and arrhythmic risk.... The resulting simulations illustrate ways in which KChIP2- and Ca2+- dependent control of IKv43 can result in a sustained outward current that can neutralize INaL in a rate- and myocyte subtype-dependent manner. Both these currents appear to play significant roles in modulating AP duration and rate dependence in midmyocardial myocytes. ... By design, these models allow upward integration into organ models or may be used as a basis for further investigations into cellular heterogeneities." See paper for more and details. | |
| Ionic basis of alternans and Timothy Syndrome (Fox et al. 2002), (Zhu and Clancy 2007) | |
| From Zhu and Clancy: "... Here we employ theoretical simulations to examine the effects of a Timothy Syndrome (TS) mutation in the L-type Ca2+ channel on cardiac dynamics over multiple scales, from a gene mutation to protein, cell, tissue, and finally the ECG, to connect a defective Ca2+ channel to arrhythmia susceptibility. ..." | |
| Midbrain dopamine neuron: firing patterns (Canavier 1999) | |
| Sodium dynamics drives the generation of slow oscillations postulated to underly NMDA-evoked bursting activity. | |
| Myelinated nerve fibre myelin resistance dependent on extracellular K+ level (Brazhe et al. 2010) | |
| Excitation leads to rise in paranodal [K]e under the myelin. This causes structural changes in myelin structure and resistance. Current model aims to simulate this aspect. This is a space-clamped model of a double-cable nerve fibre. | |
| Nigral dopaminergic neurons: effects of ethanol on Ih (Migliore et al. 2008) | |
| We use a realistic computational model of dopaminergic neurons in vivo to suggest that ethanol, through its effects on Ih, modifies the temporal structure of the spiking activity. The model predicts that the dopamine level may increase much more during bursting than pacemaking activity, especially in those brain regions with a slow dopamine clearance rate. The results suggest that a selective pharmacological remedy could thus be devised against the rewarding effects of ethanol that are postulated to mediate alcohol abuse and addiction, targeting the specific HCN genes expressed in dopaminergic neurons. | |
| Nodes of Ranvier with left-shifted Nav channels (Boucher et al. 2012) | |
| The two programs CLSRanvier.f and propagation.f simulate the excitability of a myelinated axon with injured nodes of Ranvier. The injury is simulated as the Coupled Left Shift (CLS) of the activation(V) and inactivation(V) (availability) of a fraction of Nav channels. | |
| Paradoxical GABA-mediated excitation (Lewin et al. 2012) | |
| "GABA is the key inhibitory neurotransmitter in the adult central nervous system, but in some circumstances can lead to a paradoxical excitation that has been causally implicated in diverse pathologies from endocrine stress responses to diseases of excitability including neuropathic pain and temporal lobe epilepsy. We undertook a computational modeling approach to determine plausible ionic mechanisms of GABAA-dependent excitation in isolated post-synaptic CA1 hippocampal neurons because it may constitute a trigger for pathological synchronous epileptiform discharge. In particular, the interplay intracellular chloride accumulation via the GABAA receptor and extracellular potassium accumulation via the K/Cl co-transporter KCC2 in promoting GABAA-mediated excitation is complex. ..." | |
| Regulation of firing frequency in a midbrain dopaminergic neuron model (Kuznetsova et al. 2010) | |
| A dopaminergic (DA) neuron model with a morphologicaly realistic dendritic architecture. The model captures several salient features of DA neurons under different pharmacological manipulations and exhibits depolarization block for sufficiently high current pulses applied to the soma. | |
| Regulation of the firing pattern in dopamine neurons (Komendantov et al 2004) | |
| Midbrain dopaminergic (DA) neurons in vivo exhibit two major firing patterns: single-spike firing and burst firing. The firing pattern expressed is dependent on both the intrinsic properties of the neurons and their excitatory and inhibitory synaptic inputs. Experimental data suggest that the activation of NMDA and GABAA receptors is crucial contributor to the initiation and suppression of burst firing, respectively, and that blocking calcium-activated potassium channels can facilitate burst firing. This multi-compartmental model of a DA neuron with a branching structure was developed and calibrated based on in vitro experimental data to explore the effects of different levels of activation of NMDA and GABAA receptors as well as the modulation of the SK current on the firing activity. | |
| Simulation study of Andersen-Tawil syndrome (Sung et al 2006) | |
| Patients with Andersen-Tawil syndrome (ATS) mostly have mutations on the KCNJ2 gene producing loss of function or dominant-negative suppression of the inward rectifier K(+) channel Kir2.1. However, clinical manifestations of ATS including dysmorphic features, periodic paralysis (hypo-, hyper-, or normokalemic), long QT, and ventricular arrhythmias (VA) are considerably variable. Using a modified dynamic Luo-Rudy simulation model of cardiac ventricular myocyte, we elucidate the mechanisms of VA in ATS. We adopted a kinetic model of KCNJ2 in which channel block by Mg(+2) and spermine was incorporated. In this study, we attempt to examine the effects of KCNJ2 mutations on the ventricular action potential (AP), single-channel Markovian models were reformulated and incorporated into the dynamic Luo-Rudy model for rapidly and slowly delayed rectifying K(+) currents and KCNJ2 channel. During pacing at 1.0 Hz with [K(+)]o at 5.4 mM, a stepwise 10% reduction of Kir2.1 channel conductance progressively prolonged the terminal repolarization phase of AP along with gradual depolarization of the resting membrane potential (RMP). At 90% reduction, early after- depolarizations (EADs) became inducible and RMP was depolarized to -55.0 mV (control: -90.1 mV) followed by emergence of spontaneous action potentials (SAP). Both EADs and SAP were facilitated by a decrease in [K(+)]o and suppressed by increase in [K(+)]o. beta-adrenergic stimulation enhanced delayed after-depolarizations (DADs) and could also facilitate EADs as well as SAP in the setting of low [K(+)]o and reduced Kir2.1 channel conductance. In conclusion, the spectrum of VA in ATS includes (1) triggered activity mediated by EADs and/or DADs, and (2) abnormal automaticity manifested as SAP. These VA can be aggravated by a decrease in [K(+)]o and beta-adrenergic stimulation, and may potentially induce torsades de pointes and cause sudden death. In patients with ATS, the hypokalemic form of periodic paralysis should have the highest propensity to VA especially during physical activities. | |
| Single neuron with ion concentrations to model anoxic depolarization (Zandt et al. 2011) | |
| A minimal single neuron model, including changing ion concentrations and homeostasis mechanisms. It shows the sudden depolarization that occurs after prolonged anoxia/ischemia. | |
| Sodium potassium ATPase pump (Chapman et al. 1983) | |
| The electrochemical properties of a widely accepted six-step reaction scheme for the Na,K-ATPase have been studied by computer simulation. | |
| 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. " | |
| 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. | |
ModelDB Home SenseLab Home Help
Questions, comments, problems? Email the ModelDB Administrator
How to cite ModelDB
This site is Copyright 2012 Shepherd Lab, Yale University