Activation, Nicotinic acetylcholine receptor

Text from LaLone et al. (2017) Weight of evidence evaluation of a network of adverse outcome pathways linking activaiton of the nicotinic acetylcholine receptor in honey bees to colony death. Science of the Total Environment 584-585, 751-775:

"Nicotinic acetylcholine receptors belong to the cys-loop superfamily of ligand-gated ion channels, responsible for rapid neurotransmission (Karlin, 2002). In insects nAChR have signaling roles in nervous systems and neuromuscular junctions and other cells (Jones and Sattelle, 2010; Lindstrom, 2003). Under normal conditions the endogenous neurotransmitter, acetylcholine (ACh), attaches to the ligand binding domains on the extracellular region of the pentameric nAChR. This initiates a conformation change that promotes the influx and efflux of calcium (Ca2+) and extracellular sodium and intracellular potassiumions, respectively, to create the action potential necessary for synaptic signaling (Jones and Sattelle, 2010). Activation of the nAChR, by natural or synthetic agonists, and subsequent involvement in neurotransmission is well established. Although the nAChR is conserved across vertebrates and invertebrates, the diverse composition and assembly of α-(containing two adjacent cysteine residues important in ACh binding) and non α-(lacking the cysteine residues) subunits confer diverse functional architecture and, therefore, toxicological responses (Jones and Sattelle, 2010)."

Text fromTable 2 of LaLone et al. (2017) Weight of evidence evaluation of a network of adverse outcome pathways linking activaiton of the nicotinic acetylcholine receptor in honey bees to colony death. Science of the Total Environment 584-585, 751-775:

"• Radiolabeled nAChR agonists, (e.g., [3H] imidacloprid) or nAChR subunit specific antibodies to detect location and subunit composition of nAChR • Ligand competition studies evaluating [3H] agonist displacement to determine ligand affinities to the nAChR • Whole-cell voltage clamp electrophysiological measurements with agonists to measure nAChR activation"

LaLone, C.A., Villeneuve, D.L., Wu-Smart, J., Milsk, R.Y., Sappington, K., Garber, K.V., Housenger, J. and Ankley, G.T., 2017. Weight of evidence evaluation of a network of adverse outcome pathways linking activation of the nicotinic acetylcholine receptor in honey bees to colony death. STOTEN. 584-585, 751-775.

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Lindstrom, J.M., 2003. Nicotinic acetylcholine receptors of muscles and nerves. Ann. N. Y. Acad. Sci. 998 (1), 41–52.

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LaLone, C.A., Villeneuve, D.L., Lyons, D., Helgen, H.W., Robinson, S.L., Swintek, J.A., Saari, T.W., Ankley, G.T., 2016. Sequence alignment to predict across species susceptibility (SeqAPASS): a web-based tool for addressing the challenges of cross-species extrapolation of chemical toxicity. Toxicol. Sci. 153 (2), 228–245.