API

Aop: 113

AOP Title

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Glutamate-gated chloride channel activation leading to acute mortality

Short name:

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GluCl activation to mortality

Authors

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Kellie Fay

Point of Contact

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Kellie Fay

Contributors

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  • Kellie Fay

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite Under Development 1.29 Included in OECD Work Plan


This AOP was last modified on December 03, 2016 16:37

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Revision dates for related pages

Page Revision Date/Time
Activation, Glutamate-gated chloride channel December 03, 2016 16:37
Increased, Chloride conductance September 16, 2017 10:16
hyperpolarisation, neuron September 16, 2017 10:16
N/A, Ataxia, paralysis, or hyperactivity September 16, 2017 10:16
Increased, Mortality May 15, 2017 11:34
Decreased, population 1 December 03, 2016 16:37
Activation, Glutamate-gated chloride channel leads to Increased, Chloride conductance December 03, 2016 16:38
hyperpolarisation, neuron leads to N/A, Ataxia, paralysis, or hyperactivity December 03, 2016 16:38
Increased, Mortality leads to Decreased, population 1 December 03, 2016 16:38
N/A, Ataxia, paralysis, or hyperactivity leads to Increased, Mortality December 03, 2016 16:38
Increased, Chloride conductance leads to hyperpolarisation, neuron December 03, 2016 16:38

Abstract

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Macrocylcic lactone (ML) antihelmintics, insecticides and acaricids (e.g. abamectin and ivermectin) target the alpha subunits of the glutamate-gated chloride channels (GluCl) present in nematodes, arthropods, crustaceans (daphnia), and mollusks. The binding of the ML may result in directly opening the ion channel, or may potentiate the effects of the endogenous agonist, glutamate, resulting in increased chloride entry into the cell. With the increased influx of chloride ions, the cell becomes hyperpolarized (neuron) or depolarized (myocyte), resulting in paralysis and death. Mammals do not possess glutamate-gated chloride channels, but the structure of the GluCl channel is similar to the glycine === Background (optional) ===


Background (optional)

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Summary of the AOP

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Stressors

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Molecular Initiating Event

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Title Short name
Activation, Glutamate-gated chloride channel Activation, Glutamate-gated chloride channel

Key Events

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Title Short name
Increased, Chloride conductance Increased, Chloride conductance
hyperpolarisation, neuron hyperpolarisation, neuron
N/A, Ataxia, paralysis, or hyperactivity N/A, Ataxia, paralysis, or hyperactivity

Adverse Outcome

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Title Short name
Increased, Mortality Increased, Mortality
Decreased, population 1 Decreased, population 1

Relationships Between Two Key Events (Including MIEs and AOs)

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Network View

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Life Stage Applicability

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Bombus impatiens Bombus impatiens NCBI
chaetanaphothrips orchidii chaetanaphothrips orchidii NCBI
Radopholus similis Radopholus similis NCBI
Daphnia magna Daphnia magna NCBI
Orius insidiosus Orius insidiosus NCBI
hymenoptera hymenoptera NCBI
Helicoverpa zea Helicoverpa zea NCBI
lepidoptera lepidoptera NCBI
Liriomyza trifolii Liriomyza trifolii NCBI
orius isidiosus orius isidiosus NCBI
Acyrthosiphon kondoi Acyrthosiphon kondoi NCBI

Sex Applicability

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Graphical Representation

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Click to download graphical representation template

Overall Assessment of the AOP

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Strong evidence exists for population decline in pest species (e.g., worms, ticks and mites) resulting from targeted glutamate-gated chloride channels, as well for non-target species (bees, butterflies). However, this AOP has been developed with minimal research. Given GluCl channels exist in several cell types, specific key events likely vary among species, which are not elucidated here. The review by Wolstenholme (2012) describes specific GluCl-controlled sensory inputs in worms and flies (e.g., behavioral responses to odour, temperature and light) which suggest pathways other than paralysis may be more sensitive. As such, this AOP should be considered putative with minimally-researched support.

Domain of Applicability

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Glutamate-gated chloride channels are absent in vertebrates (Slimko et al., 2002). Life Stage Applicability, Taxonomic Applicability, Sex Applicability
Elaborate on the domains of applicability listed in the summary section above. Specifically, provide the literature supporting, or excluding, certain domains.


Essentiality of the Key Events

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Weight of Evidence Summary

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Quantitative Considerations

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Considerations for Potential Applications of the AOP (optional)

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References

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Slimko, E.M., McKinney, S., Anderson, D.J., Davisodn, N., and Lester, H.A. (2002) Selective electrical silencing of mammalian neurons in vitro by the use of invertebrate ligand-gated chloride channels. J. Neurosci. 22, 7373-7379.

Wolstenholm, A. (2012) Glutamate-gated chloride channels. J. Biological Chem. 287: 48, 40232-40238.