Calcium Channel Permeation: A Field in Flux

In 1955, Alan Hodgkin and Richard Keynes published a study whose intent was to answer a rather technical question, but whose result triggered the modern analysis of ion channel permeation (Hodgkin and Keynes, 1955). They aimed to determine whether the K⁺ fluxes in giant axons followed the “Ussing flux ratio criterion,” which was then considered to indicate whether flux through a membrane occurred passively through pores. The Ussing ratio states that passive unidirectional flux should be proportional to the activity of the compound on the side from which the flux occurs. Therefore, the ratio of inward:outward unidirectional K⁺ fluxes in the axon was expected to equal the ratio of external:internal K⁺ electrochemical activities. The K⁺ fluxes in axons clearly failed the Ussing test, as Hodgkin and Keynes noted that the ratio of fluxes varied with the activity ratio raised to the 2.5th power....