Manipulation of α-Bungarotoxin Binding Sites in Nicotinic Acetylcholine Receptors to Elucidate Fundamental Aspects of Receptor Function

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Abstract:
Nicotinic acetylcholine receptors (nAChRs) mediate excitatory neurotransmission at synapses throughout the body in the neuromuscular junction and the central nervous system. The two basic types of nAChRs that have been identified and studied are the muscle nAChR and the neuronal nAChR. The neurotoxin α-bungarotoxin (Bgtx), found in the snake Bungarus multicinctus, specifically blocks muscle nAChRs and has greatly facilitated our understanding of these receptors in muscle cells. Bgtx has been used to study subunit configuration and conformation, agonist and antagonist binding, and receptor trafficking in the cell. However, many subtypes of the neuronal nAChR are not blocked by Bgtx and thus cannot be directly detected with Bgtx binding studies. One way to solve this problem is to introduce a Bgtx binding site into subunits that are not normally sensitive to Bgtx. Adding this site will allow for localization of nAChR subunits in the brain and improve our ability to study their functional properties. In this proposal, I put forth experiments to study the effect of mutations of neuronal nAChR subunits that introduce Bgtx binding sites and discuss how this approach will aid our understanding of nAChRs.
Notes:
Thesis (Ph.D. -- Brown University (2011)

Citation

Chew, Geoffrey H., "Manipulation of α-Bungarotoxin Binding Sites in Nicotinic Acetylcholine Receptors to Elucidate Fundamental Aspects of Receptor Function" (2011). Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z0V69GTV

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