Hodgkin–Huxley model Typical
action potentials are initiated by
voltage-gated sodium channels. As the
transmembrane voltage is increased the probability that a given voltage gated sodium channel is open is increased, thus enabling an influx of Na+ ions. Once the sodium inflow becomes greater than the potassium outflow, a
positive feedback loop of sodium entry is closed and thus an action potential is fired. In the early 1950s Drs.
Hodgkin and
Huxley performed experiments on the
squid giant axon, and in the process developed a model (the
Hodgkin–Huxley model) for sodium channel conductance. It was found that the conductance may be expressed as: : {g}_{Na^+} = \bar{g}_{Na^+} m^3h, where \bar{g}_{Na^+} is the maximum sodium conductance,
m is the activation gate, and
h is the inactivation gate (both gates are shown in the adjacent image). The values of
m and
h vary between 0 and 1, depending upon the transmembrane potential. As the
transmembrane potential rises, the value of
m increases, thus increasing the probability that the activation gate will be open. And as the transmembrane potential drops, the value of
h increases, along with the probability that the inactivation gate will be open. The rate of change for an
h gate is much slower than that of an
m gate, therefore if one precedes a sub-threshold voltage stimulation with a
hyperpolarizing prepulse, the value of
h may be temporarily increased, enabling the neuron to fire an action potential. Vice versa, if one precedes a supra-threshold voltage stimulation with a
depolarizing prepulse, the value of
h may be temporarily reduced, enabling the inhibition of the neuron. An illustration of how the transmembrane voltage response to a supra-threshold stimulus may differ, based upon the presence of a depolarizing prepulse, may be observed in the adjacent image. The Hodgkin–Huxley model is slightly inaccurate as it fudges over some dependencies, for example the inactivation gate should not be able to close unless the activation gate is open and the inactivation gate, once closed, is located inside the
cell membrane where it cannot be directly affected by the transmembrane potential. However, this model is useful for gaining a high level understanding of hyperpolarizing and depolarizing prepulses. Depolarizing neurons creates a more likely out come of the neuron firing.
Voltage-gated sodium channel , P -
phosphorylation, S - ion selectivity, I - inactivation, positive (+) charges in S4 are important for transmembrane voltage sensing. Since the
Hodgkin–Huxley model was first proposed in the 1950s, much has been learned concerning the structure and functionality of voltage-gated
sodium channels. Although the exact three dimensional structure of the
sodium channel remains unknown, its composition and the functionality of individual components have been determined. Voltage-gated sodium channels are large,
multimeric complexes, composed of a single α subunit and one or more β subunits, an illustration of which may be observed in the adjacent image. The α subunit folds into four homologous domains, each of which contain six α-
helical transmembrane segments. The S4 segments of each domain serve as voltage sensors for activation. Each S4 segment consists of a repeating structure of one positively charged
residue and two
hydrophobic residues, and these combine to form a helical arrangement. When the channel is
depolarized these S4 segments undergo a
conformational change that widens the helical arrangement and opens the sodium-channel
pore. Within milliseconds after the pore's opening, the intracellular loop that connects domains III and IV, binds to the channel's intracellular pore, inactivating the channel. Thus, by providing a depolarizing prepulse before a stimulus, there is a greater probability that the inactivating domains of the sodium channels have bound to their respective pores, reducing the stimulus induced sodium influx and the influence of the stimulus. ==Depolarizing prepulse properties==