On the discovery of the nicotinic acetylcholine receptor channel

Abstract

The discovery and characterization of the nicotinic acetylcholine receptor (nAChR) is in essence the story of receptor pharmacology in general; arguably one of the greatest journeys in neuroscience, spanning more than 150 years. From its beginnings as the site of action of the poison, curare, and the psychotropic drug, nicotine, to its high-resolution structure, it has touched every subfield of biology. It has shaped how transmitter-receptor interactions are analyzed quantitatively, along the way introducing the scientific community to many novel receptor concepts and kinetic mechanisms, in addition to methods, techniques, and/or their refinement, particularly for understanding single channel behavior. Important to note, is that our knowledge of fast synaptic transmission would not be the same without analysis of nAChRs at the neuromuscular junction. Although determination of nAChR function has benefited from parallel discoveries on other proteins, it can be reasonably argued that all ligand-gated ion channels have their roots somewhere in this receptor. We highlight some of the chronological steps in the discovery and characterization of the receptor, together with some of the key players.