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The action potential
  1. Mark W Barnett1,
  2. Philip M Larkman2
  1. 1Post-doctural Research Fellow Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh, UK
  2. 2Lecturer Centre for Neuroscience Research, School of Biomedical Sciences, University of Edinburgh, Edinburgh, UK
  1. Correspondence to:
 Dr M W Barnett
 Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK; M.Barnett{at}

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It is over 60 years since Hodgkin and Huxley1 made the first direct recording of the electrical changes across the neuronal membrane that mediate the action potential. Using an electrode placed inside a squid giant axon they were able to measure a transmembrane potential of around −60 mV inside relative to outside, under resting conditions (this is called the resting membrane potential). The action potential is a transient (<1 millisecond) reversal in the polarity of this transmembrane potential which then moves from its point of initiation, down the axon, to the axon terminals. In a subsequent series of elegant experiments Hodgkin and Huxley, along with Bernard Katz, discovered that the action potential results from transient changes in the permeability of the axon membrane to sodium (Na+) and potassium (K+) ions. Importantly, Na+ and K+ cross the membrane through independent pathways that open in response to a change in membrane potential.

As testimony to their pioneering work, the fundamental mechanisms described by Hodgkin, Huxley and Katz remain applicable to all excitable cells today. Indeed, the predictions they made about the molecular mechanisms that might underlie the changes in membrane permeability showed remarkable foresight. The molecular basis of the action potential lies in the presence of proteins called ion channels that form the permeation pathways across the neuronal membrane. Although the first electrophysiological recordings from individual ion channels were not made until the mid 1970s,2 Hodgkin and Huxley predicted many of the properties now known to be key components of their function: ion selectivity, the electrical basis of voltage-sensitivity and, importantly, a mechanism for quickly closing down the permeability pathways to ensure that the action potential only moves along the axon in one direction.


The resting membrane potential is essential for the normal functioning of the …

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