Electrophysiology in the Twentieth Century

Based on Walther Nernst’s equation describing the potential difference between two salt solutions of different concentrations separated by a semipermeable membrane, Julius Bernstein developed his theory of cell membrane polarization at the turn of the twentieth century. The negative electrical potential inside excitable nerve and muscle cells was due to selective permeability of the cell membrane to potassium ionsIons. Bernstein speculated that during an action potentialAction potentials, there was a brief reversible breakdown in the selective permeability allowing potassium ionsIons to enter the cell. Keith Lucas and Edgar Adrian demonstrated the “all-or-nothing principle” of nerve transmission and suggested that the action potentialAction potentials moved down the nerve by exciting the nerve region just ahead enough to propagate the signal. Development of thermionic vacuum tubesVacuum tubes for rectifying and amplifying electronic signals along with improved electrometersElectrometers allowed researchers to accurately record action potentialsAction potentials for the first time. By taking advantage of the giant squid axon that could be penetrated with a glass electrode and a new voltage-clamp technique, Allan Hodgkin and Andre Huxley determined that the action potentialAction potentials resulted from independent changes in permeability for sodium and potassium ionsIons with the conductance changing as a function of time and membrane potentialMembrane potential. They went on to develop a mathematical model based on opening and closing of ionIons channelsIon channels in the axon membrane that provided a remarkably accurate prediction of the threshold, shape, and propagation of the action potentialAction potentials. Finally, the patch-clamp technique allowed investigators to measure the current in a single ionIons channelIon channels.