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, 590 (11), 2571-5

A Brief Historical Perspective: Hodgkin and Huxley

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A Brief Historical Perspective: Hodgkin and Huxley

Christof J Schwiening. J Physiol.

Figures

Figure 1
Figure 1. The cover of the 1963 Nobel Prize Programme
Huxley, left, looks on as Hodgkin adjusts a brand-new Tektronix 502A oscilloscope. Together with John Carew Eccles (27 January 1903–2 May 1997), Andrew Fielding Huxley (22 November 1917) and Alan Lloyd Hodgkin (5 February 1914–20 December 1998) won the 1963 Nobel Prize in Physiology or Medicine ‘for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane’ Programme provided by Deborah Hodgkin.
Figure 2
Figure 2. J. Z. Young, squid and the Marine Biological Association (MBA)
A, John Zachary Young (1907–1997). His discovery of the squid giant axon in the 1930s was pivotal since it provided an electrically excitable membrane of sufficient area for Hodgkin and Huxley's experiments. B, Loligo forbesi, the long-finned squid (∼60 cm long). The giant axon allows the rapid conduction of action potentials driving the escape response. Squid image taken by David Nicholson, courtesy of the MBA, Plymouth. C, it was here at the MBA on Citadel Hill in Plymouth that Hodgkin and Huxley made their recordings from squid giant axons. 1937 photo taken from Southward AJ & Roberts EK (1987). J Mar Biol Ass UK, 67, 465–506, with permission from the MBA.
Figure 3
Figure 3. Intracellular recording of the squid giant axon action potential
A, photomicrograph of an electrode inside a squid giant axon (diameter ∼500 μm). Two views of the same axon are visible from an ingenious system of mirrors devised by Huxley. This allowed simultaneous viewing of the electrode from both front and side and was essential to avoid the electrode damaging the nerve membrane as it was threaded down the axon. Image taken from Hodgkin & Huxley (1945). B, the first intracellular recording of an action potential. The sine wave time marker has a frequency of 500 Hz. Reproduced from Hodgkin & Huxley (1939) by permission from Macmillan Publishers Ltd: Nature©1939.
Figure 4
Figure 4. A family of currents acquired using large depolarizations under voltage-clamp control
There are a few unusual features of this original recording. Both the traces and voltages have the opposite sign to the current convention, inward currents are shown plotted upwards and depolarizations are given relative to the holding potential as that of the outside with respect to the inside. The –91 mV step represents a depolarization of the inside of the nerve fibre to ∼+15 mV. Modified from Hodgkin et al. (1952).
Figure 5
Figure 5. ‘The modern history of ion channels began in 1952 when Hodgkin and Huxley published their seminal papers on the theory of the action potential in the squid giant axon …’
Roderick MacKinnon Nobel Prize Lecture, 2003. Image taken from Jiang et al. (2003). Reprinted by permission from Macmillan Publishers Ltd: Nature©2003.
Figure 6
Figure 6. Modelling the action potential
A, calculated (upper) and measured (lower) action potentials in squid giant axons. Using their qualitative descriptions of n, m and h based upon the infinity proportions and rate constants, Hodgkin and Huxley iteratively calculated the current carried by Na+ and K+ flowing across the membrane. By assuming that these currents flowed for a short period of time, they derived a new voltage. Since every iteration produced a new voltage, a new set of n, m and h variables had to be calculated for the next time step. To produce such a trace required many hundreds of iterations. Figure taken from Hodgkin & Huxley (1952e). B, the Brunsviga 20 (produced in Braunschweig by Brunsviga Maschinenwerke, Grimme, Natalis & Co.), one of the most popular mechanical calculators. It was produced up to the early 1970s and marketed with the slogan ‘Brains of Steel’. This particular one was photographed in what was Alan Hodgkin's space in the basement of the Physiological Laboratory in Cambridge and, whilst its original owner is unknown, it has belonged to Richard Adrian, then Trevor Lamb and now Hugh Robinson. Photograph taken by Christof Schwiening.

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