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Event: 559

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Activation, Nicotinic acetylcholine receptor

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Activation, Nicotinic acetylcholine receptor
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
neuron

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
acetylcholine receptor activity Nicotinic acetylcholine receptor increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
nAChR activation - colony death 1 MolecularInitiatingEvent Carlie LaLone (send email) Open for comment. Do not cite
nAChR activation - colony death/failure2 MolecularInitiatingEvent Carlie LaLone (send email) Open for comment. Do not cite
nAChR activation - colony loss 3 MolecularInitiatingEvent Carlie LaLone (send email) Open for comment. Do not cite
nAChR activation - colony loss 5 MolecularInitiatingEvent Carlie LaLone (send email) Open for comment. Do not cite
nAChR activation - colony loss 6 MolecularInitiatingEvent Carlie LaLone (send email) Open for comment. Do not cite
nAChR activation - colony loss 7 MolecularInitiatingEvent Carlie LaLone (send email) Open for comment. Do not cite
nAChR activation - colony loss 8 MolecularInitiatingEvent Carlie LaLone (send email) Open for comment. Do not cite
nAChR activation - colony loss 4 MolecularInitiatingEvent Carlie LaLone (send email) Open for comment. Do not cite
nAChR to colony loss/failure MolecularInitiatingEvent Carlie LaLone (send email) Under Development: Contributions and Comments Welcome

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

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)."

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

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"

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

References

List of the literature that was cited for this KE description. More help

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.

Karlin, A., 2002. Emerging structure of the nicotinic acetylcholine receptors. Nat. Rev. Neurosci. 3 (2), 102–114.

Jones, A.K., Sattelle, D.B., 2010. Diversity of insect nicotinic acetylcholine receptor subunits. Adv. Exp. Med. Biol. 683, 25–43.

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

Tomizawa,M., Casida, J.E., 2003. Selective toxicity of neonictinoids attributable to specificity of insect and mammalian nicotinic receptors. Annu. Rev. Entomol. 48, 339–364.

Dani, J.A., Bertrand, D.D., 2007. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system.Annu. Rev. Pharmacol. Toxicol. 47, 699–729.

Matsuda, K., Kanaoka, S., Akamatsu,M., Sattelle, D.B., 2009. Diverse actions and target-site selectivity of neonicotinoids: structural insights. Mol. Pharmacol. 76 (1), 1–10.

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.