A Neuroscience Field Guide: The squid giant axon

You are probably wondering where in your nervous system is your squid giant axon, and why I’m writing about it in the Field Guide.  Not to be confused with the giant squid axon (ie. an axon from a giant squid) the squid giant axon is a very large axon that controls escape behaviors in regular squid.  The reason it is relevant, is that it was using the giant axon from common Atlantic squid, Loligo pealeii, that Hodgkin and Huxley, figured out how nerve impulses —known as action potentials— are generated. Why use squid axons? Mainly because they’re huge. They can be up to 1 mm in diameter. This allows an experimenter to basically squeeze out the normal cytoplasm from the axon and perfuse the inside with whatever salt solution he or she pleases. Furthermore, a wire can be stuck inside the axon and used to measure electrical currents entering and leaving the axon through its membrane. This experimental preparation was first developed by JZ Young in England and then later refined by Hodgkin and Huxley as well as KS Cole in Woods Hole.

Confused neurophysiologists attempt to extract axon from giant squid.

So why are squid giant axons so large? Mainly because they need to be fast. And this brings up an important principle of what is known as cable theory: that bigger diameter axons conduct current faster. You can think of axons as a sort of leaky hose full of tiny little holes along its length. As water goes in one end of the hose it will leak out of the little holes as well as travel down the length of the tube. The more of these little holes you will have, the lower the water pressure will be at the other end of the tube. If you increase the diameter of the hose, there will be relatively more space for the water to go down the length of the tube. You will also increase the net number of holes but the cross sectional area of the hose will increase at a faster rate as you increase the hoses diameter. In an axon, charge is conducted by the salty solution inside the axon and it also leaks out of the axon through little pores known as ion channels. In a fatter axon you are adding more membrane and thus more channels, decreasing the electrical resistance of the membrane, but at the same time there is more salty solution inside the axon decreasing the electrical resistance along the length of the axon even more. Thus relatively more current will travel down the length of the axon than will leak out via the membrane. In vertebrate axons (and in some invertebrates), the nervous system has developed myelin, which is a fatty coat that covers the axon. This makes the membrane much less leaky and therefore you can have axons that are thin and also fast.

The squid giant axon also facilitated the development of an important neurophysiological technique known as the voltage-clamp. A voltage clamp allows you to set the internal voltage of a cell (or an axon in this case) at a fixed value and then measure the electrical current flowing in or out of the neuron. In order for neurons to generate electrical impulses, they need to be at a voltage which is different than the environment outside of the neuron. They can do this by maintaining a gradient of charged ions which can enter or leave the cell via ion channels, allowing the voltage of the cell to change. These rapid changes in voltage are what constitute an action potential. What the voltage clamp does is that using an electrical wire in side the axon or cell the experimenter can artificially fix the voltage of the inside of the axon and measure the current that flows through the membrane at different voltages. Using this technique Hodgkin and Huxley were able to describe the precise currents entering or leaving the cell as the voltage changed in an action potential. Since they could perfuse any type of salt solution on the inside and the outside of the squid axon, they also determined the type of ions that flux through the membrane. In this case it turned out to be sodium and potassium ions. Apparently H&H travelled to Woods Hole to learn the technique from Cole and afterwards returned to England to do their experiments. Meanwhile there was some trouble with the squid supply in Cape Cod for the remainder of that year and so H&H were able to basically finish their experiments and scoop Cole.

Recordings of voltage changes during an action potential is a squid axon. The top recording is from Curtis and Cole, 1939, and shows that as the voltage changes, the membrane resistance decreases, showing that ion channels are open. The bottom graph is from Hodgkin and Huxley, 1939 and shows the changes in membrane voltage during an action potential. Mind you these are NOT voltage clamp experiments since the voltage is changing. They are recordings of voltage changes inside the axon relative to the outside.

Thus the giant squid axon has been an incredible useful preparation that has helped us understand how nerve impulses are generated. And in addition to the giant axon, it has a giant synapse, where some of the basics underlying synaptic transmission were discovered. So next time you eat your calamari, be sure to thank your squid. And then add lots of hot sauce.

Incidentally, a documentary was made about the squid giant axon in the 70’s. The most remarkable thing about it is the hair of all these neurophysiologists. You can see some clips here.


Further Reading

Nobel acceptance speeches of Hodgkin and Huxley.

Nice little primer from the Nobel site about nerve signaling.

Cool paper on the history of electrophysiology (may require subscription).

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7 Responses to A Neuroscience Field Guide: The squid giant axon

  1. Zen Faulkes says:

    “In vertebrate axons, the nervous system has developed myelin(.)”

    There are myelinated axons in some invertebrates, too. The structure of the myelin is a bit different, but the function is the same.

    Hartline DK, Colman DR. 2007. Rapid conduction and the evolution of giant axons and myelinated fibers. Current Biology 17(1): R29-R35. http://dx.doi.org/10.1016/j.cub.2006.11.042

    • namnezia says:

      Did not know that (though I probably should have), thanks! It’s cool that myelin seems to have evolved separately several different times.

  2. Brooksphd says:

    What a loverly post! I grew up, as it were, eating this stuff as my bread and butter, but a good re-telling is always welcome.

  3. Rohan Aurora says:

    Nice read. Is there any specific reason why H&H has to choose squid giant axon for the experiments? (apart from size)

    What stuff did H&H maneuver in their paper such that it wouldn’t work for smaller axons?

    • Namnezia says:

      I think size (and the abundance of squid) was the main reason. Having such a big axon allowed them to perfuse the inside of the axon with whatever media they chose, so if they wanted to see the effect of doubling intracellular potassium, they could do this easily. Also, they needed to insert a wire electrode into the axon to provide voltage-camp control. This would be hard to do in smaller axons. Nowdays you can access the inside of teeny mammalian axons using patch-clamp recordings, but it would still be difficult to perfuse the inside completely.

  4. Pingback: Giant Squid Axon | Sabin Braaains!!!

  5. Pingback: Kraken | Rats and Pharmacists

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