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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The PC12 clone is a line of rat pheochromocytoma cells which undergoes neuronal differentiation in the presence of nerve growth factor (NGF) protein. In the absence of NGF, PC12 cells are electrically inexcitable, while after several weeks of NGF treatment, they develop sodium action potentials. The number and density of sodium channels on PC12 cells before and after treatment with NGF were estimated by measuring the binding of [3H]saxitoxin ([3H]STX). The data indicate that [3H]STX binding increases in the NGF-treated cells by 15- to 20-fold per cell, 3- to 10-fold per mg of protein, and an estimated 7-fold per unit area of membrane. The kinetic properties for [3H]STX binding are unchanged, however, by NGF treatment. A Hodgkin-Huxley analysis (Hodgkin, A. L., and A. F. Huxley (1952) J. Physiol. (Lond.) 117: 500-544) suggests that the estimated density of sodium channels in NGF-untreated PC12 cells is sufficient to explain their lack of excitability. On the other hand, the estimated channel density on the NGF-treated cells (30 to 50/micrometers 2) is comparable to that in other excitable systems. Thus, the development of excitability in PC12 cells in response to NGF could be due to the induction of sodium channel synthesis.
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PMID:Nerve growth factor-induced increase in saxitoxin binding to rat PC12 pheochromocytoma cells. 711 65

Inactivation of many ion channels occurs through largely voltage-independent transitions to an inactivated state from the open state or from other states in the pathway leading to opening of the channel. Because this form of inactivation is state-dependent rather than voltage-dependent, it cannot be described by the standard Hodgkin-Huxley formalism used in virtually all modeling studies of neuronal behavior. Using two examples, cumulative inactivation of the Kv3 potassium channel and inactivation of the fast sodium channel, we extend the standard formalism for modeling macroscopic membrane currents to account for state-dependent inactivation. Our results provide an accurate description of cumulative inactivation of the Kv3 channel, new insight into inactivation of the sodium channel, and a general framework for modeling macroscopic currents when state-dependent processes are involved. In a model neuron, the macroscopic Kv3 current produces a novel short-term memory effect and firing delays similar to those seen in hippocampal neurons.
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PMID:Modeling state-dependent inactivation of membrane currents. 752 8

It has recently become apparent that in the dendrites or short axons of some neurons, voltage-dependent sodium channels are used not to generate action potentials but to modulate graded potentials; graded potentials carry far more information than do action potentials. A model axon (or dendrite) is described in which sodium channels with kinetics described by equations of the Hodgkin-Huxley type boost conduction of small voltage signals. For a sodium channel density beyond a certain minimum there exists an optimal potential, depolarized with respect to the resting potential, at which there is no steady-state decrement along the axon. For an axon not longer than about 0.7 length constants, small, steady-state deviations from this optimal potential imposed at one end of the axon appear amplified in a graded and stable way at the other end. A small pulse of potential is propagated with amplification and more rapidly than in an axon with a passive membrane. Compared to passive propagation, there will be an improvement in signal-to-noise ratio at the synapse; the axon also acts as a selective frequency filter. The same axon is capable of conducting an action potential.
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PMID:Conditions under which Na+ channels can boost conduction of small graded potentials. 771 6

The sodium channel plays essential roles in the initiation and propagation of action potentials (APs) in excitable tissues including the heart, nerves, and muscles. Na channels in these tissues undergo so-called activation and then inactivation upon step-depolarizations of the cell membrane. Hodgkin and Huxley, early in the 1950s, proposed a mathematical model to describe such events, which was based on voltage-clamp (V-C) data on axonal membranes. However, for the next 30 years or so since the pioneering work of the above workers, electrophysiological studies of the Na channel kinetics in the heart had relied exclusively on AP data (Vmax) as an indirect measure of the Na current instead of V-C data due to difficulty in determining V-C from the complex geometry of cardiac tissues. However, recent development of an isolation procedure for preparing single heart cells and the use of single patch-pipettes for high resolution V-C experiments on these cells have made direct recording of Na channel currents also possible in the heart. Voltage-clamp studies carried out for the last decade have provided several lines of evidence supporting the view that the Na channel properties in the heart of any animal species are somehow more complex than in the axonal membrane and hence showing that Hodgkin-Huxley model can not be directly applied to describe the Na channel behavior in the former type of tissues. Here, we review recent results from V-C studies on Na channel properties with special reference to the macroscopic Na current in cardiac tissues.
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PMID:[Gating properties of cardiac Na channels: from the macroscopic Na current viewpoint]. 839 56

In olfactory mitral cells, dual patch recordings show that the site of action potential initiation can shift between soma and distal primary dendrite and that the shift is dependent on the location and strength of electrode current injection. We have analyzed the mechanisms underlying this shift, using a model of the mitral cell that takes advantage of the constraints available from the two recording sites. Starting with homogeneous Hodgkin-Huxley-like Na(+)-K(+) channel distribution in the soma-dendritic region and much higher sodium channel density in the axonal region, the model's channel kinetics and density were adjusted by a fitting algorithm so that the model response was virtually identical to the experimental data. The combination of loading effects and much higher sodium channel density in the axon relative to the soma-dendritic region results in significantly lower "voltage threshold" for action potential initiation in the axon; the axon therefore fires first unless the voltage gradient in the primary dendrite is steep enough for it to reach its higher threshold. The results thus provide a quantitative explanation for the stimulus strength and position dependence of the site of action potential initiation in the mitral cell.
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PMID:Computational analysis of action potential initiation in mitral cell soma and dendrites based on dual patch recordings. 1060 36

This paper proposes a new double-chamber model (DCM) of ion channels. The model ion channel consists of a series of three pores alternating with two chambers. The chambers are net negatively charged. The chamber's electric charge originates from dissociated amino acid side chains and is pH dependent. The chamber's net negative charge is compensated by cations present inside the chamber and in a diffuse electric layer outside the chamber. The pore's permeability is constant independent of time. One pore of the sodium channel and one of the potassium channel is a voltage-sensing pore. Due to the channel's structure, ions flow through the pores and chambers in a time-dependent manner. The model reproduces experimental voltage clamp and action potential data. The current flowing through a single sodium channel is less then one femtoampere. The DCM is considerably simpler then the Hodgkin and Huxley model (HHM) used to describe the electrophysiological properties of an axon. Unlike the HHM, the DCM can explain refractoriness, anode break excitation, accommodation and the effect of pH and temperature on the channels without additional parameters. In the DCM, the axon membrane shows repetitive activity depending on the channel density, sodium to potassium channel ratio and external potassium concentration. In the DCM, the action potential starts from 'hot spot areas' of higher channel densities and a higher sodium to potassium channel ratio, and then propagates through the whole axon.
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PMID:A new double-chamber model of ion channels. Beyond the Hodgkin and Huxley model. 1294 15

The squid giant axon is the canonical experimental membrane prototype for the study of action potential generation. This work is concerned with Clay's model for this preparation, which implements the nonlinear dependence of sodium and potassium currents on voltage, a multicompartmental description of sodium channel kinetics that takes into account the dependence between activation and inactivation, revised potassium activation function, and potassium accumulation in the axoplasm and its uptake by glial cells. This model accounts better than the standard Hodgkin-Huxley (HH) model for the response of squid giant axons to various stimuli. We systematically compare the responses of the Clay model and the standard HH model to pulse-like and constant current stimuli. We also analyze hybrid models that combine features from both models. These studies reveal that the differences between the sodium currents account for the main difference between the two models, namely the lower excitability of the Clay model.
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PMID:Excitability of the Clay model for squid giant axon. 1456 16

Calculations using the Hodgkin-Huxley and one-dimensional cable equations have been performed to determine the expected sensitivity of conduction and refractoriness to changes in the time constant of sodium channel deactivation at negative potentials, as reported experimentally by Rosen (Bioelectromagnetics 24 (2003) 517) when voltage-gated sodium channels are exposed to a 125 mT static magnetic field. The predicted changes in speed of conduction and refractory period are very small.
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PMID:The effects of static magnetic field on action potential propagation and excitation recovery in nerve. 1555 68

The (standard) FitzHugh reduction of the Hodgkin-Huxley equations for the propagation of nerve impulses ignores the dynamics of the activation gates. This assumption is invalid and leads to an over-estimation of the wave speed by a factor of 5 and the wrong dependence of wave speed on sodium channel conductance. The error occurs because a non-dimensional parameter, which is assumed to be small in the FitzHugh reduction, is in fact large (approximately 18). We analyse the Hodgkin-Huxley equations for propagating nerve impulses in the limit that this non-dimensional parameter is large, and show that the analytical results are consistent with numerical simulations of the Hodgkin-Huxley equations.
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PMID:A note on the asymptotic reduction of the Hodgkin-Huxley equations for nerve impulses. 1599 89

The influence of intrinsic channel noise on the spontaneous spiking activity of poisoned excitable membrane patches is studied by use of a stochastic generalization of the Hodgkin-Huxley model. Internal noise stemming from the stochastic dynamics of individual ion channels is known to affect the collective properties of the whole ion channel cluster. For example, there exists an optimal size of the membrane patch for which the internal noise alone causes a regular spontaneous generation of action potentials. In addition to varying the size of ion channel clusters, living organisms may adapt the densities of ion channels in order to optimally regulate the spontaneous spiking activity. The influence of a channel block on the excitability of a membrane patch of a certain size is twofold: first, a variation of ion channel densities primarily yields a change of the conductance level; second, a down-regulation of working ion channels always increases the channel noise. While the former effect dominates in the case of sodium channel block resulting in a reduced spiking activity, the latter enhances the generation of spontaneous action potentials in the case of a tailored potassium channel blocking. Moreover, by blocking some portion of either potassium or sodium ion channels, it is possible to either increase or decrease the regularity of the spike train.
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PMID:Effect of channel block on the spiking activity of excitable membranes in a stochastic Hodgkin-Huxley model. 1620 23


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