Modeling the Excitability of Mammalian Nerve Fibers: Influence of Afterpotentials on the Recovery Cycle

2002 ◽  
Vol 87 (2) ◽  
pp. 995-1006 ◽  
Author(s):  
Cameron C. McIntyre ◽  
Andrew G. Richardson ◽  
Warren M. Grill

Human nerve fibers exhibit a distinct pattern of threshold fluctuation following a single action potential known as the recovery cycle. We developed geometrically and electrically accurate models of mammalian motor nerve fibers to gain insight into the biophysical mechanisms that underlie the changes in axonal excitability and regulate the recovery cycle. The models developed in this study incorporated a double cable structure, with explicit representation of the nodes of Ranvier, paranodal, and internodal sections of the axon as well as a finite impedance myelin sheath. These models were able to reproduce a wide range of experimental data on the excitation properties of mammalian myelinated nerve fibers. The combination of an accurate representation of the ion channels at the node (based on experimental studies of human, cat, and rat) and matching the geometry of the paranode, internode, and myelin to measured morphology (necessitating the double cable representation) were needed to match the model behavior to the experimental data. Following an action potential, the models generated both depolarizing (DAP) and hyperpolarizing (AHP) afterpotentials. The model results support the hypothesis that both active (persistent Na+ channel activation) and passive (discharging of the internodal axolemma through the paranodal seal) mechanisms contributed to the DAP, while the AHP was generated solely through active (slow K+ channel activation) mechanisms. The recovery cycle of the fiber was dependent on the DAP and AHP, as well as the time constant of activation and inactivation of the fast Na+ conductance. We propose that experimentally documented differences in the action potential shape, strength-duration relationship, and the recovery cycle of motor and sensory nerve fibers can be attributed to kinetic differences in their nodal Na+ conductances.

Author(s):  
Nicole A Pelot ◽  
David C. Catherall ◽  
Brandon J. Thio ◽  
Nathan D. Titus ◽  
Edward D. Liang ◽  
...  

Biophysically-based computational models of nerve fibers are important tools for designing electrical stimulation therapies, investigating drugs that affect ion channels, and studying diseases that affect neurons. Although peripheral nerves are primarily composed of unmyelinated axons (i.e., C-fibers), most modeling efforts focused on myelinated axons. We implemented the single-compartment model of vagal afferents from Schild et al. 1994 and extended the model into a multi-compartment axon, presenting the first cable model of a C-fiber vagal afferent. We also implemented the updated parameters from Schild and Kunze 1997. We compared the responses of these novel models to three published models of unmyelinated axons (Rattay and Aberham 1993; Sundt et al. 2015; Tigerholm et al. 2014) and to experimental data from single fiber recordings. Comparing Schild et al. 1994 and 1997 revealed that differences in rest potential and action potential shape were driven by changes in maximum conductances rather than changes in sodium channel dynamics. Comparing the five model axons, the conduction speeds and strength-duration responses were largely within expected ranges, but none of the models captured the experimental threshold recovery cycle-including a complete absence of late subnormality in the models-and their action potential shapes varied dramatically. The Tigerholm et al. 2014 model best reproduced the experimental data, but these modeling efforts make clear that additional data are needed to parameterize and validate future models of autonomic C-fibers.


Author(s):  
V.V. Gorskiy ◽  
A.G. Loktionova

In order to compute the intensity of laminar-turbulent heat transfer, algebraic or differential models are commonly used, which are designed to compute the contribution of turbulent pulsations to the transfer properties of the gas. This, in turn, dictates the necessity of validating these semi-empirical models against experimental data obtained under conditions simulating the gas dynamics inherent to the phenomenon as observed in practice. The gas dynamic patterns observed during gradient flow around fragments of aircraft structure (such as a sphere or a cylinder) differs qualitatively from the patterns revealed by the flow around the lateral surfaces of these fragments, which necessitates using various semi-empirical approaches in this case, followed by mandatory validation against the results of respective experimental studies. In recent years, there appeared scientific publications dealing with modifying one of the algebraic models designed to compute the contribution of turbulent pulsations in the boundary layer to the transfer properties of the gas; this was accomplished by making use of experimental data obtained for a hemisphere at extremely high Reynolds numbers. The paper proposes a similar modification of the same turbulence model, based on fitting a wide range of experimental data obtained for lateral surfaces of spherically blunted cones. As a result of the investigations conducted, we stated a method for computing laminar-to-turbulent heat transfer over the entire surface of a blunted cone; the accuracy of the method is acceptable in terms of most practical applications. We show that the computational method presented is characterised by minimum error as compared to the most widely spread methods for solving this problem


2020 ◽  
Vol 31 ◽  
pp. 01004 ◽  
Author(s):  
Tatyana Nesterova ◽  
Konstantin Ushenin ◽  
Dmitry Shmarko ◽  
Olga Solovyova

Age-related changes in human cardiomyocytes are closely related to cardiac diseases, especially atrial fibrillation. Restricted availability of biological preparations from the human atrial myocardium complicates experimental studies on the aging processes in cardiomyocytes. In this preliminary study, we used available experimental data on the age-related changes in ionic conductances in canine atrial cardiomyocytes to predict possible consequences of similar remodeling in humans using two mathematical models (Courtemanche98 and Maleckar09) of human atrial cardiomyocytes. The study was performed using the model population approach, allowing one to assess variability in the cellular response to different interventions affecting model parameters. Here, this approach was used to evaluate the effects of age-related parameter modulation on action potential biomarkers in the two models. Simulation results show a significant decrease in the action potential duration and membrane potential at 20% of the action potential duration in aging. These model predictions are consistent with experimental data from mammalians. The action potential characteristics are shown to serve as notable biomarkers of age-related electrophysiological remodeling in human atrial cardiomyocytes. A comparison of the two models shows different behavior in the prediction of repolarization abnormalities.


1979 ◽  
Vol 6 (3) ◽  
pp. 337 ◽  
Author(s):  
M.J Beilby ◽  
H.G.L Coster

An analysis, based on the Hodgkin-Huxley (H-H) equations is given of excitation processes in the plasmalemma of cells of C. corallina. Voltage clamp data for the plasmalemma show the presence of two activation and two inactivation processes and both of these transients are modelled in a manner analagous to the gated Na+ current in squid axons. Separation of the various ionic components of the experimental clamp currents was achieved by fitting the experimental data over a wide range of potentials to the model equations. The potential dependencies of the various H-H parameters for C. corallina, determined from the analysis of experimental results, are presented. A reconstruction is also given of the action potential and it is shown to be in satisfactory agreement with the experimental data. Comparisons are made of the experimental and predicted threshold potential, refractory period and the effects of the external Cl- and Ca�+ ion concentrations on the action potential. From the H-H parameters, the time courses during an action potential of the conductances g*Cl, g*x (� g*Ca?), the non activated/inactivated steady-state conductance g*ss, and the corresponding ionic currents I*Cl, I*x (� I*Ca?) and I*ss are calculated. While in the H-H analysis the peak value of g*x is found to be very large (larger than the peak value of g*Cl), it is shown that nevertheless I*Cl and I*ss dominate during an action potential.


2004 ◽  
Vol 91 (1) ◽  
pp. 571-575 ◽  
Author(s):  
Jason J. Kuo ◽  
Martijn Schonewille ◽  
Teepu Siddique ◽  
Annet N. A. Schults ◽  
Ronggen Fu ◽  
...  

ALS (amyotrophic lateral sclerosis) is an adult-onset and deadly neurodegenerative disease characterized by a progressive and selective loss of motoneurons. Transgenic mice overexpressing a mutated human gene (G93A) coding for the enzyme SOD1 (Cu/Zn superoxide dismutase) develop a motoneuron disease resembling ALS in humans. In this generally accepted ALS model, we tested the electrophysiological properties of individual embryonic and neonatal spinal motoneurons in culture by measuring a wide range of electrical properties influencing motoneuron excitability during current clamp. There were no differences in the motoneuron resting potential, input conductance, action potential shape, or afterhyperpolarization between G93A and control motoneurons. The relationship between the motoneuron's firing frequency and injected current (f-I relation) was altered. The slope of the f-I relation and the maximal firing rate of the G93A motoneurons were much greater than in the control motoneurons. Differences in spontaneous synaptic input were excluded as a cause of increased excitability. This finding identifies a markedly elevated intrinsic electrical excitability in cultured embryonic and neonatal mutant G93A spinal motoneurons. We conclude that the observed intrinsic motoneuron hyperexcitability is induced by the SOD1 toxic gain-of-function through an aberration in the process of action potential generation. This hyperexcitability may play a crucial role in the pathogenesis of ALS as the motoneurons were cultured from presymptomatic mice.


2011 ◽  
Vol 29 (1) ◽  
pp. 69-80 ◽  
Author(s):  
N. Yu. Orlov ◽  
O.B. Denisov ◽  
O.N. Rosmej ◽  
D. Schäfer ◽  
Th. Nisius ◽  
...  

AbstractTheoretical and experimental studies of radiative properties of substances heated by pulsed current devises or lasers and used as X-ray sources have been carried out depending on plasma conditions, and specific spectra of X-ray absorption and radiation for different materials have been calculated. Important features of the theoretical model, known as the ion model of plasma, are discussed. This model can be applied for calculations of the radiative properties of complex materials over a wide range of plasma parameters. For purposes of indirect-driven inertial fusion based on the hohlraum concept, an optimization method is used for the selection of an effective complex hohlraum wall material, which provides high radiation efficiency at laser interaction with the wall. The radiation efficiency of the resulting material is compared with the efficiency of other composite materials that have previously been evaluated theoretically. A similar theoretical study is performed for the optically thin X-pinch plasma produced by exploding wires. Theoretical estimations of radiative efficiency are compared with experimental data that have been obtained from measurements of X-pinch radiation energy yield using two exploding wire materials, NiCr and Alloy 188. It is shown that the theoretical results agree well with the experimental data. A symmetric multilayer X-pinch, where W and Mo wires are used, is as well considered. The theoretical explanation of experimental phenomena is discussed based on the W and Mo radiative spectra. The ion model was as well applied for interpretation of experimental results on opacities of CHO-plasma obtained via indirect heating of low density polymer layers by means of soft X-rays. The new diagnostics method based on the deformation of the of the Carbon absorption K-edge when foam layer is heated to plasma is discussed. The spectral coefficients for X-ray absorption in CHO-plasma are calculated in the photon energy region around the Carbon K-edge for different plasma temperatures and mean foam density. In this case, the Carbon K-edge position on the energy scale can be used for plasma temperature diagnostic.


Author(s):  
Heecheon You

This study examined the severity of carpal tunnel syndrome symptoms in relation to nerve conduction measures of the median nerve. The symptom scales include (1) numbness, (2) tingling, (3) nocturnal symptoms, (4) pain, (5) weakness, and (6) clumsiness; the nerve conduction measures are (1) peak amplitude and (2) peak latency of the sensory action potential, (3) conduction velocity of the sensory nerve fibers, (4) peak amplitude and (5) onset latency of the motor action potential. The symptom severity and nerve conduction impairment were evaluated for 34 affected hands of 24 patients (6 males and 18 females) by using a questionnaire developed by Levine et al. and an electromyographic instrument, respectively. Significant relationships identified among the clinical scales resulted in a dichotomous symptom classification scheme with a criterion of the relatedness to nerve damage: primary and secondary symptoms. Correlation analysis on the symptom and electrodiagnostic measures showed both the severity scales for the primary and all the symptoms had higher correlations with the extent of the nerve injury than that for the secondary symptoms. These results demonstrated a biological significance of the clinical scales, which can be used in evaluating the outcome of treatments and developing a model for exposure-severity relationship.


1998 ◽  
Vol 538 ◽  
Author(s):  
Silva K. Theiss ◽  
M.-J. Caturla ◽  
T. Diaz de la Rubia ◽  
M.C. Johnson ◽  
Ant Uralt ◽  
...  

AbstractWe have developed a kinetic Monte Carlo (kMC) simulator that links atomic migration and binding energies determined primarily from first principles calculations to macroscopic phenomena and laboratory time scales. Input for the kMC simulation is obtained from a combination of ab initio planewave pseudopotential calculations, molecular dynamics simulations, and experimental data. The simulator is validated against an extensive series of experimental studies of the diffusion of B spikes in self-implanted Si. The implant energy, dose, and dose rate, as well as the detailed thermal history of the sample, are included. Good agreement is obtained with the experimental data for temperatures between 750 and 950°C and times from 15 to 255 s. At 1050°C we predict too little diffusion after 105 s compared to experiment: apparently, some mechanism which is not adequately represented by our model becomes important at this temperature. Below 1050°C, the kMC simulation produces a complete description over macroscopic time scales of the atomic level diffusion and defect reaction phenomena that operate during the anneals. This simulator provides a practical method for predicting technologically interesting phenomena, such as transient enhanced diffusion of B, over a wide range of conditions, using energetics determined from first-principles approaches.


2021 ◽  
Author(s):  
S. V. Pankov ◽  
V. N. Korzhnev ◽  
V. I. Mileshin ◽  
V. A. Fateev

Abstract The paper presents the results of aeromechanical design of a large-scale model stage for a high-efficient low-noise fan designed for an advanced civil geared turbofan engines with ultra-low rotational speeds of rotor blades (313.4 m/s), high flow specific capacity (up to 202 kg/m2/s) and high bypass ratio (13.5). Total pressure ratio in the bypass duct of the fan model stage is 1.38. To ensure the experimental studies, characteristics are calculated from choking to a surge line within a wide range of rotational speeds. For the studies of the experimental fan model (EFM), a design project is developed and used in manufacturing a fan stage with 0.7-m rotor diameter for tests at the C-3A acoustic test facility. The manufacturing technology for blades made of polymer composite materials (PCM) is of particular importance. Rotor blades of the geared fan model are made of PCM. The analysis of experimental data and their comparison with the computation results within the range of corrected rotational speeds from 0.325 to 1.0 are presented. At first, only gas-dynamic and strength characteristics of the stage are studied. The analysis shows a good agreement of calculated integral parameters with the experimental data. Acoustic performances of the EFM will be studied later on.


2021 ◽  
Vol 74 (11-12) ◽  
pp. 397-407
Author(s):  
Murat Alemdar

Conventional parameters used in electrodiagnosis of ulnar neuropathy at elbow (UNE) are: (i) absolute across-elbow ulnar nerve motor conduction velocity (MCV), (ii) reduction rate of composed muscle action potential (CMAP) amplitude from above to below elbow stimulation, and (iii) MCV difference between forearm and across-elbow segment. We aimed to search the diagnostic accuracy values of these parameters on UNE, and their correlations with axonal dysfunction of ulnar nerve fibers. Arms with clinical signs of UNE and two-fold healthy controls were included. We detected the best cut off points of the measured parameters and their possible combinations. Their diagnostic accuracy values and correlations with parameters reflecting the axonal functions were analyzed, statistically. Totally, 118 arms with UNE and 236 controls were included. Absolute across-elbow MCV yielded a higher accuracy than MCV difference and reduction rate of CMAP amplitude (p = 0.010 and p˂0.001, respectively). Besides, combining it with other parameters did not increase the diagnostic yield. Correlation analyses revealed that the only parameter having positive linear correlations with sensory nerve action potential amplitudes both in the control and the disease groups is the absolute across-elbow MCV. The absolute across-elbow MCVs have also positive linear correlation with CMAP amplitudes in disease group. The absolute across-elbow MCV is the most valuable conventional parameter for the electrodiagnosis of UNE. It is also the most correlated parameter with the electrodiagnostic parameters reflecting the axonal functions of the ulnar nerve fibers.


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