9515330 Johnson The neuromuscular junction is a critical relay point in the flow of information from the central nervous system to muscles in all vertebrate animals. Motor neurons ending at these junctions release the neurotransmitter, acetylcholine, which diffuses a short distance to interact with molecular receptor molecules, the acetylcholine receptors. These critical receptors are channel pores that open when activated by acetylcholine, thereby initiating the cascade of events that leads to muscle contraction. Through funding of this grant experiments are carried out to determine the detailed structure of acetylcholine receptors, which can be obtained in large quantities from the electric ray. The approach is that of quantitative fluorescence spectroscopy, a unique technique for studying structural features of intact acetylcholine receptor molecules. The experiments are meant to delineate the specific binding sites of inhibitors substances and thus to enhance the understanding of how these bindine sites change as the acetylcholine receptor pore opens and closes. This study should significantly contribute to the development of a molecular understanding of the actions of chemicals on the acetylcholine receptor. Such understanding will provide insights into how this critically important protein functions at a molecular level. Concepts and experimental approaches developed in the study of the acetylcholine receptor will be applicable to the vast array of other neurotransmitter and hormone receptors found in all animals.
