Nicotinic receptors containing α4 and β2 subunits constitute a major family of CNS receptors to acetylcholine (ACh). α4β2 receptors modulate release of neurotransmitters, and tune a variety of circuits including those that regulate cognitive function. Disruptions in cholinergic transmission have significant consequences for human health. Activation and up-regulation of receptors by nicotine leads to addiction, and reduced expression of α4β2 receptors has been implicated in Alzheimer’s and Parkinson’s diseases. Our research is focused on an investigation of the functional properties of desformylflustrabromine (dFBr), a novel compound that selectively potentiates α4β2 responses to ACh via an allosteric mechanism. We are using single-channel methods to obtain a detailed understanding of the mechanisms that underlie dFBr-mediated modulation of two stoichiometric forms of α4β2 receptors (expressed in HEK cells) that may have distinct functional roles in vivo. Completion of these objectives will aid in determining the potential use of dFBr as a probe of the functional roles of nicotinic receptors in vivo, and as a therapeutic agent to correct errors in cholinergic signaling that contribute to disease.
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- B.S. 1985, Stanford University
- Ph.D. 1990, Columbia University
Brian W. Edmonds
Department of Chemistry and Biochemistry
900 Yukon Dr.
University of Alaska Fairbanks
Fairbanks, AK 99775-6160