Brian Edmonds
Chemistry & Biochemistry
University of Alaska Fairbanks
United States of America
Biography
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
Research Interest
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.
Publications
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olquhoun, D., Hawkes, A.G., Merlushkin, A. and Edmonds, B. (1997) Properties of single ion channel currents elicited by a pulse of agonist concentration or voltage. Phil. Trans. R. Soc. Lond. A 355, 1743
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Silver, R.A., Colquhoun, D., Cull-Candy, S.G. and Edmonds, B. (1996) Deactivation and desensitization of non-NMDA receptors in patches and the time course of EPSCs in rat cerebellar granule cells. J.Physiol. (Lond) 493, 167.
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Edmonds, B. and Colquhoun, D. (1992) Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration. Proc. Roy. Soc. Lond. B 250, 279.
