A quantitative description of membrane current and its application to conduction and excitation in nerve
TL;DR: This article concludes a series of papers concerned with the flow of electric current through the surface membrane of a giant nerve fibre by putting them into mathematical form and showing that they will account for conduction and excitation in quantitative terms.
Abstract: This article concludes a series of papers concerned with the flow of electric current through the surface membrane of a giant nerve fibre (Hodgkinet al, 1952,J Physiol116, 424–448; Hodgkin and Huxley, 1952,J Physiol116, 449–566) Its general object is to discuss the results of the preceding papers (Section 1), to put them into mathematical form (Section 2) and to show that they will account for conduction and excitation in quantitative terms (Sections 3–6)
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TL;DR: This work presents the basic ideas that would help informed users make the most efficient use of NEURON, the powerful and flexible environment for implementing models of individual neurons and small networks of neurons.
Abstract: The moment-to-moment processing of information by the nervous system involves the propagation and interaction of electrical and chemical signals that are distributed in space and time. Biologically realistic modeling is needed to test hypotheses about the mechanisms that govern these signals and how nervous system function emerges from the operation of these mechanisms. The NEURON simulation program provides a powerful and flexible environment for implementing such models of individual neurons and small networks of neurons. It is particularly useful when membrane potential is nonuniform and membrane currents are complex. We present the basic ideas that would help informed users make the most efficient use of NEURON.
2,617 citations
Cites methods from "A quantitative description of membr..."
...Short course: Using the NEURON Simulation Environment © 10/97 MLH and NTC all rights reserved In this model the soma and axon contain HodgkinHuxley (HH) sodium, potassium, and leak channels (Hodgkin and Huxley 1952), while the dendrites have constant, linear (“passive”) ionic conductances....
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...Short course: Using the NEURON Simulation Environment © 10/97 MLH and NTC all rights reserved In this model the soma and axon contain HodgkinHuxley (HH) sodium, potassium, and leak channels (Hodgkin and Huxley 1952), while the dendrites have constant, linear (“passive”) ionic conductances....
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30 May 2008
TL;DR: Comparisons can now be made between the kinetics of the ionic conductances as described by Hodgkin & Huxley, and the steady-state distribution and kinetic changes of the charged controlling particles, which should lead to useful conclusions about the intramolecular organization of the sodium channels and the conformational changes that take place under the influence of the electric field.
Abstract: The ionic channels in excitable membranes are of two classes: those that open and close when the membrane potential alters and those that respond to the release of an appropriate chemical transmitter. The former are responsible for the conduction of impulses in nerve and muscle fibres and the latter for synaptic transmission. It is now clear that the sodium and potassium channels in electrically excitable membranes are functionally distinct, since each can be blocked without affecting the behaviour of the other. It has recently proved possible to study, in the voltage-clamped squid giant axon, the movements of the mobile charges or dipoles that form the voltage-sensitive portion of the sodium channels, which give rise to the so-called 'gating' current. Detailed comparisons can now be made between the kinetics of the ionic conductances as described by Hodgkin & Huxley, and the steady-state distribution and kinetics of the charged controlling particles, which should lead to useful conclusions about the intramolecular organization of the sodium channels and the conformational changes that take place under the influence of the electric field. There is as yet little information about the chemical nature of the electrically excitable channels, but significant progress has been made towards the isolation and characterization of the acetylcholine receptors in muscle and electric organ.
2,489 citations
TL;DR: The biological plausibility and computational efficiency of some of the most useful models of spiking and bursting neurons are discussed and their applicability to large-scale simulations of cortical neural networks is compared.
Abstract: We discuss the biological plausibility and computational efficiency of some of the most useful models of spiking and bursting neurons. We compare their applicability to large-scale simulations of cortical neural networks.
2,396 citations
TL;DR: How noise affects neuronal networks and the principles the nervous system applies to counter detrimental effects of noise are highlighted, and noise's potential benefits are discussed.
Abstract: Noise — random disturbances of signals — poses a fundamental problem for information processing and affects all aspects of nervous-system function. However, the nature, amount and impact of noise in the nervous system have only recently been addressed in a quantitative manner. Experimental and computational methods have shown that multiple noise sources contribute to cellular and behavioural trial-to-trial variability. We review the sources of noise in the nervous system, from the molecular to the behavioural level, and show how noise contributes to trial-to-trial variability. We highlight how noise affects neuronal networks and the principles the nervous system applies to counter detrimental effects of noise, and briefly discuss noise's potential benefits.
2,350 citations
TL;DR: The identity of the ions which carry the various phases of the membrane current is chiefly concerned with sodium ions, since there is much evidence that the rising phase of the action potential is caused by the entry of these ions.
Abstract: In the preceding paper (Hodgkin, Huxley & Katz, 1952) we gave a general description of the time course of the current which flows through the membrane of the squid giant axon when the potential difference across the membrane is suddenly changed from its resting value, and held at the new level by a feed-back circuit ('voltage clamp' procedure). This article is chiefly concerned with the identity of the ions which carry the various phases of the membrane current. One of the most striking features of the records of membrane current obtained under these conditions was that when the membrane potential was lowered from its resting value by an amount between about 10 and 100 mV. the initial current (after completion of the quick pulse through the membrane capacity) was in the inward direction, that is to say, the reverse ofthe direction of the current which the same voltage change would have caused to flow in an ohmic resistance. The inward current was of the right order of magnitude, and occurred over the right range of membrane potentials, to be the current responsible for charging the membrane capacity during the rising phase of an action potential. This suggested that the phase of inward current in the voltage clamp records might be carried by sodium ions, since there is much evidence (reviewed by Hodgkin, 1951) that the rising phase of the action potential is caused by the entry of these ions, moving under the influence of concentration and potential differences. To investigate this possibility, we carried out voltage clamp runs with the axon surrounded by solutions with reduced sodium concentration. Choline was used as an inert cation since replacement of sodium with this ion makes the squid axon completely inexcitable, but does not reduce the resting potential (Hodgkin & Katz, 1949; Hodgkin, Huxley & Katz, 1949).
2,315 citations
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TL;DR: A theoretical picture has been presented based on the use of the general kinetic equations for ion motion under the influence of diffusion and electrical forces and on a consideration of possible membrane structures that shows qualitative agreement with the rectification properties and very good agreementwith the membrane potential data.
Abstract: Impedance and potential measurements have been made on a number of artificial membranes. Impedance changes were determined as functions of current and of the composition of the environmental solutions. It was shown that rectification is present in asymmetrical systems and that it increases with the membrane potential. The behavior in pairs of solutions of the same salt at different concentrations has formed the basis for the studies although a few experiments with different salts at the same concentrations gave results consistent with the conclusions drawn. A theoretical picture has been presented based on the use of the general kinetic equations for ion motion under the influence of diffusion and electrical forces and on a consideration of possible membrane structures. The equations have been solved for two very simple cases; one based on the assumption of microscopic electroneutrality, and the other on the assumption of a constant electric field. The latter was found to give better results than the former in interpreting the data on potentials and rectification, showing agreement, however, of the right order of magnitude only. Although the indications are that a careful treatment of boundary conditions may result in better agreement with experiment, no attempt has been made to carry this through since the data now available are not sufficiently complete or reproducible. Applications of the second theoretical case to the squid giant axon have been made showing qualitative agreement with the rectification properties and very good agreement with the membrane potential data.
2,685 citations
TL;DR: The identity of the ions which carry the various phases of the membrane current is chiefly concerned with sodium ions, since there is much evidence that the rising phase of the action potential is caused by the entry of these ions.
Abstract: In the preceding paper (Hodgkin, Huxley & Katz, 1952) we gave a general description of the time course of the current which flows through the membrane of the squid giant axon when the potential difference across the membrane is suddenly changed from its resting value, and held at the new level by a feed-back circuit ('voltage clamp' procedure). This article is chiefly concerned with the identity of the ions which carry the various phases of the membrane current. One of the most striking features of the records of membrane current obtained under these conditions was that when the membrane potential was lowered from its resting value by an amount between about 10 and 100 mV. the initial current (after completion of the quick pulse through the membrane capacity) was in the inward direction, that is to say, the reverse ofthe direction of the current which the same voltage change would have caused to flow in an ohmic resistance. The inward current was of the right order of magnitude, and occurred over the right range of membrane potentials, to be the current responsible for charging the membrane capacity during the rising phase of an action potential. This suggested that the phase of inward current in the voltage clamp records might be carried by sodium ions, since there is much evidence (reviewed by Hodgkin, 1951) that the rising phase of the action potential is caused by the entry of these ions, moving under the influence of concentration and potential differences. To investigate this possibility, we carried out voltage clamp runs with the axon surrounded by solutions with reduced sodium concentration. Choline was used as an inert cation since replacement of sodium with this ion makes the squid axon completely inexcitable, but does not reduce the resting potential (Hodgkin & Katz, 1949; Hodgkin, Huxley & Katz, 1949).
2,315 citations
TL;DR: The importance of ionic movements in excitable tissues has been emphasized by a number of recent experiments which are consistent with the theory that nervous conduction depends on a specific increase in permeability which allows sodium ions to move from the more concentrated solution outside a nerve fibre to the more dilute solution inside it.
Abstract: The importance of ionic movements in excitable tissues has been emphasized by a number of recent experiments. On the one hand, there is the finding that the nervous impulse is associated with an inflow of sodium and an outflow of potassiuim (e.g. Rothenberg, 1950; Keynes & Lewis, 1951). On the other, there are experiments which show that the rate of rise and amplitude of the action potential are determined by the concentration of sodium in the external medium (e.g. Hodgkin & Katz, 1949 a; Huxley & Stiimpffi, 1951). Both groups of experiments are consistent with the theory that nervous conduction depends on a specific increase in permeability which allows sodium ions to move from the more concentrated solution outside a nerve fibre to the more dilute solution inside it. This movement of charge makes the inside of the fibre positive and provides a satisfactory explanation for the rising phase of the spike. Repolarization during the falling phase probably depends on an outflow of potassium ions and may be accelerated by a process which increases the potassium permeability after the action potential has reached its crest (Hodgkin, Huxley & Katz, 1949).
1,569 citations
TL;DR: This paper contains a further account of the electrical properties of the giant axon of Loligo and deals with the 'inactivation' process which gradually reduces sodium permeability after it has undergone the initial rise associated with depolarization.
Abstract: This paper contains a further account of the electrical properties of the giant axon of Loligo. It deals with the 'inactivation' process which gradually reduces sodium permeability after it has undergone the initial rise associated with depolarization. Experiments described previously (Hodgkin & Huxley, 1952a, b) show that the sodium conductance always declines from its initial maximum, but they leave a number of important points unresolved. Thus they give no information about the rate at which repolarization restores the ability of the membrane to respond with its characteristic increase of sodium conductance. Nor do they provide much quantitative evidence about the influence of membrane potential on the process responsible for inactivation. These are the main problems with which this paper is concerned. The experimental method needs no special description, since it was essentially the same as that used previously (Hodgkin, Huiley & Katz, 1952; Hodgkin & Huxley, 1952b).
1,547 citations
1,349 citations