In a 1976 reminiscence of his landmark work with Andrew Huxley that elucidated the ionic basis of the action potential, Alan Hodgkin made a puzzling admission:
Why were Hodgkin and Huxley so disappointed with their work? Through a brilliant train of thought that considered the linearity of the current-voltage curve and the relative amplitudes of ionic and gating currents (Hodgkin and Huxley, 1952), they concluded that the Na+ current which drives the action potential passes through a channel—defined as a pore that passes ions at high rates compared to enzyme or carrier turnover. It is often forgotten that this disproved their working hypothesis. Reasoning that the high selectivity of the molecule responsible for Na+ permeation was inconsistent with high flux, they had predicted a Na+-selective carrier, not a pore (Hodgkin et al., 1949; also, see Fig. 7 in Hodgkin, 1976,...
