Sir Alan Hodgkin and Sir Andrew Huxley
Two neuroscientists made some ground-breaking discoveries that would not have been possible without the help of a few molluscs
It may seem unlikely that a squid could be a major contributor to our knowledge of the human nervous system today. But two neuroscientists, Alan Hodgkin (1914–1998) and Andrew Huxley (1917–2012), made some ground-breaking discoveries thanks to the mollusc.
In the 1930s, it was generally accepted that the nerve impulse was an all-or-nothing event controlled by the membrane potential (the difference in electrical potential between the interior and exterior of the cell).
The change in potential generated at each point on the nerve fibre was known to somehow spread forwards and stimulate the next section of the fibre. It was not known how the potential changed so drastically or how it spread along the fibre – and this is what Hodgkin and Huxley set out to discover.
In 1935, Alan Hodgkin began his research into electrical impulses, called action potentials, in nerve cells, just as Andrew Huxley began his undergraduate degree, both at Cambridge University. After Huxley had completed his degree, he joined Hodgkin at a marine centre in Plymouth as a research partner to begin work on the ionic mechanisms of the cell.
A marine centre may seem a strange place to carry out research on nerve fibres, but a particular aquatic species appeared to hold the answer to Hodgkin and Huxley’s questions: the squid.
The squid years
The squid has a complex nervous system and contains very large axons. The axon is the long, thin projection of the nerve cell that conducts electrical impulses away from the main body of the neuron, and it can be up to 1 mm in diameter in a squid.
In humans, the diameter of the largest axon measures 0.1 mm, and to study this size of neuron at the time was difficult. Being bigger, squid neurons made it much easier for Hodgkin and Huxley to develop a model for the movement of ions in a nerve cell during an impulse.
(The reason axons in squid are bigger is because they do not have myelin sheaths. Lack of myelination slows down action potential transmission; squid axons make up for this by being much wider, as this facilitates faster transmission.)
The scientists directly measured the potential across the membrane and saw that it became substantially positive during an action potential. This was against the theory at that time and was a breakthrough for Hodgkin and Huxley.
By varying the concentration of various ions inside the neuron, they saw that these concentrations were what controlled the permeability of the cell membrane (how easy it is for ions to pass from the inside to the outside of the cell). They then saw that as this permeability changed through the axon, the potential changed along it, transporting the nerve impulse along the neuron.
In effect, they discovered how an action potential is transferred through the cell. At rest, a neuron is more negatively charged inside the cell than outside. During an action potential, sodium channels in the membrane of the cell are triggered to open and sodium ions rush in. When the inside of the cell reaches a certain concentration – the threshold – neighbouring sodium channels are triggered to open. This continues down the length of the neuron, reversing the charge so the inside of the cell is now more positive, passing the action potential down the cell.
Because of the start of World War II, Hodgkin and Huxley had to postpone their research for several years. They left the Plymouth marine centre just two days before Hitler invaded Poland. Hodgkin worked on aviation medicine and airborne radar, and Huxley concentrated his research on firearms. The marine centre was badly bombed, meaning Hodgkin and Huxley could not continue their research until 1948.
In 1952 they published five papers describing the experiments they had conducted and their results, ultimately leading to the mathematical model for an action potential. They received the Nobel Prize in Physiology or Medicine in 1963 owing to the influence of their model on neurology as a whole.Lead image:
N Seery/Wellcome Images
Questions for discussion
- Do you think using animals for medical research is justified? Why? (You can use the BBC article below to help you decide.)