The nicotinic acetylcholine receptor is a multisubunit protein with an integral ion channel. The binding of acetylcholine to its receptor site, on excitable membranes of nerve and muscle cells, causes the ion channel to open, allowing small cations to enter the cell. As a result of cation entry, the cell membrane becomes depolarized. The nicotinic acetylcholine receptor has a number of binding sites for ligands that regulate the receptor's function. The purpose of this research project is to understand the molecular events that occur during channel activation, by studying the relationship between the structure and dynamics of acetylcholine-like molecules, known as agonists, and the specific steps leading to the opening of the ion channel. Experiments utilizing radioligand binding, electrophysiological recording, nuclear magnetic resonance spectroscopy and computational chemistry techniques will be performed to study the detailed molecular interactions between agonists and receptor. Because the acetylcholine receptors and number of structurally related ligand-gated ion channels are important transducers of information in the nervous system, a better comprehension of the molecular events associated with channel activation is crucial to the understanding of the nervous system in general.
