The crucial decade that ion channels were proven to exist : The vision of Bertil Hille and Clay Armstrong and how it came through.

Abstract

This retrospective begins with the first recording of the Na⁺ and K⁺ currents underlying the action potential in the giant squid axon reported by Hodgkin and Huxley in 1952, which made the question of where ions pass through the membrane more compelling. The notion of channels in the membrane had been around for quite some time but was so vague and contested that even the recording of Na⁺ and K⁺ currents through the membrane was not considered sufficient proof of their existence. In fact, Hodgkin and Huxley never referred to ion channels in their papers, only currents and conductances. The word "channel" remained somewhat left out from the scientific debate for almost another two decades, even though its idea was slowly making its way into the minds of discerning scientists. It is precisely this period that the present retrospective focuses on to understand the evolution of the ion channel concept from a speculative functional entity to a physical transmembrane object that serves the efficient and selective passage of ions. In this regard, the fundamental contribution of Bertil Hille and Clay Armstrong in promoting this idea, in the cold attitude, when not open aversion, of much of the scientific community, is fully acknowledged. Mention should also be made of Erwin Neher and Bert Sakmann's patch-clamp technique, which made it possible to directly measure ion currents through individual channels, thus conclusively demonstrating their presence in cell membranes. The retrospective goes on to briefly show how the cloning of ion channels in the 1980s and the first X-ray crystallographic structures at the turn of the century fully confirmed the initial suggestions, and closes by illustrating the relevance of ion channels in biology and medicine.