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George P. Hess     (WEB PAGE) gph2 @ cornell.edu 216 Biotechnology Building      607-255-4809   [edit] Faculty Department: Molecular Biology and Genetics Field: Biochemistry, Molecular, and Cell Biology; Biophysics; Chemistry and Chemical Biology; Pharmacology Keywords: caged neurotransmitters (1), Cell and Molecular Neuroscience (23), Ion channel (6), Ligand-activated ion channels (2), Neurotransmitter receptors and transporters (9), Patch clamp (2) We are investigating the structure and function of membrane-bound proteins (neurotransmitter receptors) that control and integrate communication between the cells of the nervous system. Malfunction of the receptors is implicated in many diseases of the nervous system, and the receptor proteins are the targets of a large class of clinically important compounds and abused drugs. Until recently investigation of the mechanism of action of these receptor proteins has been hampered by the lack of techniques with adequate time resolution (microseconds-to-milliseconds). My group has developed new biophysical techniques, most recently a laser-pulse photolysis method using caged neruotranmsitters, for investigating the receptors in cells isolated from specific areas of the nervous system to fill this gap. When a neurotransmitter binds to the active receptor forms, ion-conducting receptor-channels open, initiating electrical signals that transmit information in the nervous system. Whether or not a signal is transmitted depends on the concentration of open receptor-channels. This in turn depends on the neurotransmitter concentration and the length of time receptors are exposed to it. The immediate goal is to determine quantitative models, on a physiologically relevant time scale, for the chemical kinetic reactions of excitatory and inhibitory neurotransmitter [acetylcholine, gamma-aminobutyric acid, (GABA), glycine, glutamate, N-methyl-D-aspartate (NMDA) and serotonin receptors]. This goal has already been achieved with the nicotinic acetylcholine receptor from the electric organ (modified muscle) of certain fish. The eventual aim is to integrate all the available information into a consistent mechanism of signal transmission in the mammalian central nervous system. The chemical mechanism of neurotransmitter receptor-mediated reactions is expected to set limits to the various hypotheses concerning the operation of neuronal circuits and brain function, and to lead to an understanding of the effects of pharmacological agents and abused drugs on receptor function. An interdisciplinary approach, involving physical and organic chemistry, instrument development, molecular biology, electrophysiology, cellular neurobiology, and computer simulation, is being used to achieve these aims.

Please report corrections, questions, comments, and problems to: Lori Miller (lmm8 AT cornell.edu)