The Hodgkin-Huxley Model is a scientific model that describes how action potentials in neurons are initiated and propagated. It is a set of nonlinear ordinary differential equations that approximates the electrical characteristics of excitable cells such as neurons and cardiac myocytes.
Alan Lloyd 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.
The components of a typical Hodgkin-Huxley model are shown in the figure. Each component of an excitable cell has a biophysical analog. The lipid bilayer is represented as a capacitance (Cm). Voltage-gated ion channels are represented by nonlinear electrical conductances (gn, where n is the specific ion channel), meaning that the conductance is voltage and time-dependent. This was later shown to be mediated by voltage-gated cation channel proteins, each of which has an open probability that is voltage-dependent. Leak channels are represented by linear conductances (gL). The electrochemical gradients driving the flow of ions are represented by batteries (En and EL), the values of which are determined from the Nernst potential of the ionic species of interest. Finally, ion pumps are represented by current sources (Ip).
The time derivative of the potential across the membrane () is proportional to the sum of the currents in the circuit. This is represented as follows:
where Ii denotes the individual ionic currents of the model.
Ionic Current Characterization
The current flowing through the ion channels is mathematically represented by the following equation:
where is the reversal potential of the i-th ion channel.
In voltage-gated ion channels, the channel conductance gi is a function of both time and voltage (gn(t,V) in the figure), while in leak channels gi is a constant (gL 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.
Voltage-Gated Ion Channels
Under the Hodgkin-Huxley formulation, conductances for voltage-gated channels (gn(t,V)) are expressed as:
where and are gating variables for activation and inactivation, respectively, representing the fraction of the maximum conductance available at any given time and voltage. is the maximal value of the conductance. and are constants and and are the time constants for activation and inactivation, respectively. and are the steady state values for activation and inactivation, respectively, and are usually represented by Boltzmann equations as functions of .
In order to characterize voltage-gated channels, the equations will be fit to voltage-clamp data. For a derivation of the Hodgkin-Huxley equations under voltage-clamp see. Briefly, when the membrane potential is held at a constant value (i.e., voltage-clamp), for each value of the membrane potential the nonlinear gating equations reduce to linear differential equations of the form:
Thus, for every value of membrane potential, , the following equation can be fit to the current curve:
Leak channels account for the natural permeability of the membrane to ions and take the form of the equation for voltage-gated channels, where the conductance is a constant.
Pumps and Exchangers
The membrane potential depends upon the maintenance of ionic concentration gradients across it. The maintenance of these concentration gradients requires active transport of ionic species. The sodium-potassium and sodium-calcium exchangers are the best known of these. Some of the basic properties of the Na/Ca exchanger have already been well-established: the stoichiometry of exchange is 3 Na+:1 Ca2+ and the exchanger is electrogenic and voltage-sensitive. The Na/K exchanger has also been described in detail.
Improvements to the Model
Since the publication of the original model, other versions have been developed. Some of these take into account new knowledge of the workings of neurons. Others were developed to be computationally more efficient. One such version was proposed by Richard FitzHugh and is now known as the FitzHugh-Nagumo model.
Problems and Alternative Models
The Hodgkin-Huxley model is widely accepted in the scientific community. However some problems remain:
- It can be experimentally observed that a signal traveling along a neuron results in a slight local thickening of the membrane and a force acting outwards; this should lead to a change in capacity which is not captured by the model.
- An action potential traveling along a neuron results in a slight increase in temperature followed by a decrease. The decrease cannot be explained by the Hodgkin-Huxley model, as electrical charges traveling through a resistor always produce heat.
- ^ Hodgkin, A., and Huxley, A. (1952): A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 117:500–544. PMID 12991237
- ^ Marquardt, D. (1963): An algorithm for the least-squares estimation of nonlinear parameters. SIAM J. Appl. Math. 11 (2):431–441.
- ^ Levenberg, K. (1944): A method for the solution of certain non-linear problems in least-squares. Q. Appl. Math. 2 (2):164–168.
- ^ Johnston, D., and Wu, S. (1997): Foundations of Cellular Neurophysiology, chapter 6. MIT Press, Cambridge, MA. ISBN 0-262-10053-3
- ^ Hille, B. (2001): Ionic Channels of Excitable Membranes (3rd ed.). Sinauer Associates, Inc., Sunderland, MA. ISBN 0-87893-321-2
- 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.
- Java applet of the HH Equations Numerically solves the Hodgkin-Huxley Equations. Parameters may be varied, and allows for user to select from any arbitrary current.