One of the articles we read in my biophysics class was a 1942 article by Curtis and Cole. At the time, those working on the electrical properties of neurons were in agreement that during the action potential the membrane did not simply ‘depolarize’ (i.e., lost its electrical polarization) but that it rather reverted its potential: during the action potential the inside of the neuron became more positive than the outside.
Researchers were looking at how this happened, and looking for the ions involved in setting up both the resting potential and the action potential.
In 1942 Curtis and Cole reported on an experiment in which they changed the extracellular concentration of potassium and measured the effects this had on resting and action potentials:
What they saw when they measured the amplitude of the action potential was that as they increased the concentration of potassium outside the cell, the amplitude of the action potential was reduced. But they failed to control for what turned up to be an important variable: Sodium. The way they reduced the concentration of potassium was by replacing it with sodium. Their data could be interpreted in two ways: that the amplitude of the action potential was decreased as potassium concentration was increased or that the amplitude of the action potential was decreased as sodium was decreased. This may not have been a huge oversight on their part given the state of knowledge of the time, but turned out to be a big mistake (and one that they should have controlled for).
In 1949 they showed that the ion carrying the current during the action potential was indeed sodium, something that would become known as the sodium hypothesis. Future work by Hodgkin and co-workers would define the mathematical functions that described the electrical properties of neurons, models that continue to be used today.
In 1963 Hodgkin shared the Nobel prize with his collaborator Andrew Huxley and John Eccles. My friends from the biophysics course always wondered how things would have turned out had Curtis and Cole realized the effect of sodium.
- Curtis, HJ and Cole KS (1942) Membrane Resting and Action Potentials from the Squid Giant Axon. Journal of Cellular and Comparative Physiology Vol 19 (2) 135-144
- Hodgkin AL and Katz B (1949) The effect of Sodium Ions on the Electrical Activity of the Giant Axon of the Squid. J. Physiol. 108, 37-77 (PMID: 16991839)
#SciFoo lightning talk [reloaded]