Hodgkin and Huxley

Alan Hodgkin and his young fellow Andrew Huxley discovered in 1952, the ionic composition of the action potential, that happens during the nervous impulse.

One of their first accomplishments was to measure and stablish the speed of the nervous impulse, that turned out to be 27 meters in a second (m/s). This new data suggested that what flowed through the nerves were not electrons, it had to be something else, because it was known that electrons travel at the speed of light.

Some other kind of charges had to be the responsible. The most abundant charges in cells were ions, so it seemed pretty obvious that they were involved in the matter.

The next answer they had to respond was the following: Among the different types of ions found in cells, wich ones are involved in the nervous impulse?

It was known at the time, that in a resting state, the neuron had different levels of ions inside and outside of its membrane. Inside there is more potassium, and outside there’s more sodium. The difference in charge, leads to a measurable electric potential of -70 mV. The value is negative because the charge inside the cell is more negative than it is outside. In its resting state a neuron is POLARISED.

It was also known that neurons shoot their action potential when the membrane DEPOLARISES, that is, when the value of the potencial is less negative.

At the time, it was understood that this happened because the membrane opened, somehow, letting all types of ions pass trough, allowing the concentration of ions inside and outside the cell to tend towards equilibrium.
Because the interior of the neuron was more negative, more positive ions will go inside. This would be equivalent to a short-circuit in electrical terms.

Hodgkin and Huxley didn’t accept this, short-circuit idea, because they found it to be a contradiction. During the action potencial the membrane not only turns out to be less negative, it reaches positive values. If charges were in equilibrium, as it was hypothesized, the membrane potential would be 0 mV.

It wasn’t possible that the membrane opened letting in and out ions indiscriminately. So they assumed that a selective mechanism should be involved.

When a spontaneous process happens, the chemical concentrations of each ion in both sides of the membrane, tend to equilibrate. If just one type of ion was selected to cross the membrane, this equilibrium could go on, in a way that the net difference of charge inside and outside, would create a positive potential.

Fig 1. Neural Computation
(From: Mark C.W. van Rossum, M. Hennig, 1989)

To prove their interpretation, the creation of an artefact was necessary.  This occurred in 1897. The artefact was the cathode ray oscilloscope, that permits the measure of changes In the electric potential across time.

Hodgkin and Huxley were able to amplify the currents in neurons. They were able to appreciate the changes during the action potential. To register these currents, they designed electrodes, thin tubes of glass that contained an isotonic solution. The electrodes were inserted through the membrane and had access to the interior of the nervous fiber.

Fig 2. Giant axon

To perform their study they found the axon of squid suitable for this precise job, because it can measure up to 1 mm of diameter.

It seemed logical that sodium was the selected ion, because it was the most abundant.

It was hypothesized that when there was less sodium outside of the cell, the action potencial would also be less powerful, because it was less the quantity available to go inside the cell.

This was the case, during depolarization, a flood of sodium, cross to the interior of the, making its charge positive (+30mV).

Then, repolarization happened, an inverse flood of potassium, from the interior of the cell to the exterior, restore the negative charge of the neuron, putting it into a resting state.

Phases of the action potential

Fig 3. Action potential
(From: http://www.psy.plymouth.ac.uk)

1.Membrane starts in a resting state, POLARISED, with a membrane potential around -60 mV – 70 mV. 

2. Then sodium ion channels open, the diffusion towards the inside of the cell starts, in favor of chemical gradient.

3.Then, the membrane DEPOLARISES, it’s less negative than it was, if we compare it with the exterior of the cell.

4. Now it’s around -50 mV, this is the threshold value.At this point, voltage-gated sodium ion channels open massively, and many sodium goes into the cell, until the cell becomes positively charged.

5. The potential difference across the membrane is around +40 mV. At this point, sodium ion channels close, and potassium ion channels open.The repolarization takes place, because potassium ions diffuse out of the cell creating a concetration difference, and making the cell negatively charged again.

6. Hyperpolarisation happens when the potential difference overshoots a little.The cell goes back to its resting state when its potential difference it’s restored.

Hodgkin and Huxley formulated a mathematical model that could be used to predict voltage signals from the flow of ions. This model was very precise, reason why Hodgkin and Huxley’s experiments were considered an indirect demonstration of the existence of selective ion channels in the membrane of neurons. This movements in the concentration of ions inside and outside the cell were the base of the action potential.

All this insight into how the action potential works, and the mathematical model that summarizes and predicts how this process happens, is a contribution of great importance to the foundation of modern Neuroscience.

This new information, resolved that nervous fibers, work as cables that transmit information, and the messages they transport in the form of electrical signals, could reach every last corner of our nervous systems.

This contribution made Hodgkin and Huxley, deservedly, win the Nobel Prize for medicine or physiology in 1963.

References

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