Answer: They developed a model to explain the ionic conductances observed during initiation and conduction of the action potential. Alan Hodgkin and Andrew Huxley were two English physiologists who pioneered some of the first experiments into modeling the function and behavior of neurons using electrophysiology.
What is the Hodgkin Huxley model?
Hodgkin-Huxley Models. The core mathematical framework for modern biophysically based neural modeling was developed half a century ago by Sir Alan Hodgkin and Sir Andrew Huxley. They carried out an elegant series of electrophysiological experiments on the squid giant axon in the late 1940s and early 1950s.
Who were Alan Hodgkin and Andrew Huxley?
Working together in 1939, and again from 1946 to 1952, Alan Hodgkin and Andrew Huxley formed one of the most productive and influential collaborations in the history of physiology.
When was the Huxley-Hodgkin theory published?
The theory was the culmination of an intense experimental and theoretical collaboration between Hodgkin and Huxley, from 1938 to the publication in 1952 of their five landmark papers in the Journal of Physiology. The stage was set by four key developments.
What is the Huxley model of action potentials?
Alan Hodgkin and Andrew Huxley described the model in 1952 to explain the ionic mechanisms underlying the initiation and propagation of action potentials in the squid giant axon. They received the 1963 Nobel Prize in Physiology or Medicine for this work.
What information did the Hodgkin and Huxley model provide?
The Hodgkin–Huxley model, or conductance-based model, is a mathematical model that describes how action potentials in neurons are initiated and propagated. It is a set of nonlinear differential equations that approximates the electrical characteristics of excitable cells such as neurons and muscle cells.
What did Hodgkin and Huxley Discover 1939?
Finally, Hodgkin, Huxley and Katz (following Cole and Marmont) developed a voltage-clamp circuit to enable quantitative measurement of ionic currents from squid axon.
Why is the Hodgkin-Huxley model important?
Abstract. Hodgkin and Huxley (H-H) model for action potential generation has held firm for half a century because this relatively simple and experimentally testable model embodies the major features of membrane nonlinearity: namely, voltage-dependent ionic currents that activate and inactivate in time.
Who discovered the action potential?
Julius BernsteinJulius Bernstein, with the help of Emil du Bois-Reymond, found a way to overcome these technical limitations and in about 1865 made the first recordings of the time course of the action potential.
What is the strength of Hodgkin Huxley model?
The Hodgkin-Huxley model is stimulated by a short, but strong, current pulse between t=1 and t=2 ms. The time course of the membrane potential u(t) for t>2ms shows the action potential (positive peak) followed by a relative refractory period where the potential is below the resting potential urest (dashed line).
Why did Hodgkin and Huxley use squid?
Hodgkin and Huxley chose the giant squid axon as a model system for their experiments, since it is unusually large (around 0.5 mm in diameter) and therefore quite suitable for electrophysiological experiments [1].
Who discovered the voltage clamp?
Kenneth ColeIn the late 1940s, at the University of Chicago, Kenneth Cole, with the help of George Marmont, invented an electronic circuit called a voltage clamp,2 which was used to investigate ionic conduction in nerves.
What method did Hodgkin and Huxley invent in order to determine the ionic currents that mediated the action potential?
voltage-clamp techniqueThe sodium current that initiates the nerve action potential was discovered by Hodgkin and Huxley using the voltage-clamp technique in their landmark series of papers in 1952.
Who was Alan Hodgkin and Andrew Huxley?
Working together in 1939, and again from 1946 to 1952, Alan Hodgkin and Andrew Huxley formed one of the most productive and influential collaborations in the history of physiology.
Who discovered Hodgkin lymphoma?
Hodgkin Lymphoma (HL) Thomas Hodgkin who, in 1832, described several cases of people with symptoms of a cancer involving the lymph nodes. The disease was called "Hodgkin's disease" until it was officially renamed "Hodgkin lymphoma" in the late 20th century.
What was the impact of Hodgkin and Huxley's work?
The effect of Hodgkin and Huxley's work was tremendous, leading to an explosion of interest in electrophysiology. The voltage-clamp technique began to be used on a range of large cells. However, it was Neher and Sakmann's development of the patch-clamp in the 1970s that allowed the first recordings of single ion channels from even the smallest of cells. Such recordings of these small currents were impossible using the valve-based amplifiers of 1949, and equally they would not have been possible in the 1970s without Hodgkin and Huxley's pioneering work. However, the impact of their work extended well beyond experimental electrophysiology. The Hodgkin–Huxley model contained within it probabilistic representations of the activation and inactivation of ionic conductances. In 1955 Hodgkin and Keynes published data that predicted that K + channels would be occupied by multiple ions simultaneously ( Hodgkin & Keynes, 1955 ). The molecular structural description of K + channels, confirming this prediction, won Rod MacKinnon the 2003 Nobel prize in Chemistry (see Fig. 5 ). Indeed, the ideas and equations behind their model are now the standard building blocks of neuronal modelling software for both teaching and research.
What did Huxley do in 1939?
2 ). Eventually in August 1939, after weeks of waiting, the trawlers operating beyond Plymouth Sound began to bring in catches of squid.
Why are two views of the same axon visible?
This allowed simultaneous viewing of the electrode from both front and side and was essential to avoid the electrode damaging the nerve membrane as it was threaded down the axon. Image taken from Hodgkin & Huxley (1945).
How did Huxley measure the viscosity of the axoplasm?
Huxley started by trying to measure the viscosity of axoplasm by observing the passage of mercury droplets through it , but the experiments were not a great success ( Huxley, 2004 ). The droplets sat obstinately at the top of cut axons, descending only if the axoplasm was damaged.
How many currents are there in Hodgkin's model?
Hodgkin and Huxley thus emerged with a model which incorporated four currents (capacitance, K +, Na + and leak). These, when iteratively summed to give a total current, I, predict the action potential time course with remarkable accuracy. The three voltage- and time-dependent, but otherwise uncoupled ‘variables’ ( n, m and h ), which define the proportion of the K + and Na + channels available as a proportion of the maximum available conductance ( and ) at any given time within the trajectory of an action potential, underlie the model's elegance.
What was the significance of the 1952 landmark papers?
The landmark papers of 1952 heralded the start of the modern era of biological research in general. Simple qualitative descriptions of how things might work were being replaced by quantitative modelling that could predict, in a robust fashion, the behaviour of non-linear feedback systems.
When was the Brunsviga 20 made?
It was produced up to the early 1970s and marketed with the slogan ‘Brains of Steel’.
What is the Hodgkin-Huxley theory?
The Hodgkin-Huxley theory of the action potential. The Hodgkin-Huxley (H-H) theory of the action potential, formulated 50 years ago, remains one of the great success stories in biology, and ranks among the most significant conceptual breakthroughs in neuroscience. Together with the artificial neural networks of McCulloch and Pitts, ...
What is the H-H theory?
The Hodgkin-Huxley (H-H) theory of the action potential, formulated 50 years ago, remains one of the great success stories in biology, and ranks among the most significant conceptual breakthroughs in neuroscience. Together with the artificial neural networks of McCulloch and Pitts, the quantal theory of Katz, and the cable theory of Rall, all developed at around the same time, the H-H theory provided the foundation for modern computational neuroscience.
Why was the squid axon important?
First, they chose the right model system. The squid axon offered technical advantages due to its size and relative simplicity, with only two types of voltage-gated conductances. Second, the H-H model introduced the power of computers for solving quantitative problems in neuroscience.
What is the H-H model?
The H-H model was so elegant and unprecedented in the quantitative and complete nature of its description that it provided an intellectual framework for biophysical and modeling work that would influence the field for decades.
Who developed the action potential theory?
The stage was set by four key developments. First, Cole and Curtis demonstrated that the action potential is associated ...
Who developed neural modeling?
The core mathematical framework for modern biophysically based neural modeling was developed half a century ago by Sir Alan Hodgkin and Sir Andrew Huxley. They carried out an elegant series of electrophysiological experiments on the squid giant axon in the late 1940s and early 1950s. The squid giant axon is notable for its extraordinarily large diameter (~0.5 mm). Most axons in the squid nervous system and in other nervous systems are typically at least 100 times thinner. The large size of the squid giant axon is a specialization for rapid conduction of action potentials that trigger the contraction of the squid’s mantle when escaping from a predator. In addition to being beneficial for the squid, the large diameter of the giant axon was beneficial for Hodgkin and Huxley because it permitted manipulations that were not technically feasible in smaller axons that had been used in biophysical studies up to that point. In a well-designed series of experiments, Hodgkin and Huxley systematically demonstrated how the macroscopic ionic currents in the squid giant axon could be understood in terms of changes in Na+ and K+ conductances in the axon membrane. Based on a series of voltage-clamp experiments, they developed a detailed mathematical model of the voltage-dependent and time-dependent properties of the Na+ and K+ conductances. The empirical work lead to the development of a coupled set of differential equations describing the ionic basis of the action potential (Hodgkin and Huxley, 1952), which became known as the Hodgkin-Huxley (HH) model. The real predictive power of the model became evident when Hodgkin and Huxley demonstrated that numerical integration of these differential equations (using a hand-cranked mechanical calculator!) could accurately reproduce all the key biophysical properties of the action potential. For this outstanding achievement, Hodgkin and Huxley were awarded the 1963 Nobel Prize in Physiology and Medicine (shared with Sir John Eccles for his work on the biophysical basis of synaptic transmission).
How does the HH model work?
Each individual ion channel can be thought of as containing one or more physical gates that regulate the flow of ions through the channel. An individual gate can be in one of two states, permissive or non-permissive. When all of the gates for a particular channel are in the permissive state, ions can pass through the channel and the channel is open. If any of the gates are in the non-permissive state, ions cannot flow and the channel is closed. Although it might seem more natural to speak of gates as being open or closed, a great deal of confusion can be avoided by consistently using the terminology permissive and non-permissive for gates while reserving the terms open and closed for channels.
Work
The nervous system in people and animals consists of many different cells. In cells, signals are conveyed by small electrical currents and by chemical substances.
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Andrew Fielding Huxley
The Nobel Prize in Physiology or Medicine 1963 was awarded jointly to Sir John Carew Eccles, Alan Lloyd Hodgkin and Andrew Fielding Huxley "for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane."
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Overview
The Hodgkin–Huxley model, or conductance-based model, is a mathematical model that describes how action potentials in neurons are initiated and propagated. It is a set of nonlinear differential equations that approximates the electrical characteristics of excitable cells such as neurons and cardiac myocytes. It is a continuous-time dynamical system.
Basic components
The typical Hodgkin–Huxley model treats each component of an excitable cell as an electrical element (as shown in the figure). The lipid bilayer is represented as a capacitance (Cm). Voltage-gated ion channels are represented by electrical conductances (gn, where n is the specific ion channel) that depend on both voltage and time. Leak channels are represented by linear conductances (gL). The electrochemical gradients driving the flow of ions are represented by volt…
Ionic current characterization
In voltage-gated ion channels, the channel conductance is a function of both time and voltage ( in the figure), while in leak channels, , it is a constant ( in the figure). The current generated by ion pumps is dependent on the ionic species specific to that pump. The following sections will describe these formulations in more detail.
Using a series of voltage clamp experiments and by varying extracellular sodium and potassium …
Mathematical properties
The Hodgkin–Huxley model can be thought of as a differential equation system with four state variables, , and , that change with respect to time . The system is difficult to study because it is a nonlinear system and cannot be solved analytically. However, there are many numerical methods available to analyze the system. Certain properties and general behaviors, such as limit cycles, can …
Improvements and alternative models
The Hodgkin–Huxley model is regarded as one of the great achievements of 20th-century biophysics. Nevertheless, modern Hodgkin–Huxley-type models have been extended in several important ways:
• Additional ion channel populations have been incorporated based on experimental data.
• The Hodgkin–Huxley model has been modified to incorporate transition state theory and produce ther…
See also
• Action potential
• Anode break excitation
• Autowave
• Biological neuron model
• Biological neural network
Further reading
• Hodgkin AL, Huxley AF (April 1952). "Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo". The Journal of Physiology. 116 (4): 449–72. doi:10.1113/jphysiol.1952.sp004717. PMC 1392213. PMID 14946713.
• Hodgkin AL, Huxley AF (April 1952). "The components of membrane conductance in the giant axon of Loligo". The Journal of Physiology. 116 (4): 473–96. doi:10.1113/jphysiol.1952.sp004718. PMC 1392209. PMID 14946714.
External links
• Interactive Javascript simulation of the HH model Runs in any HTML5 – capable browser. Allows for changing the parameters of the model and current injection.
• Interactive Java applet of the HH model Parameters of the model can be changed as well as excitation parameters and phase space plottings of all the variables is possible.