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Aop: 96

AOP Title

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Axonal sodium channel modulation leading to acute mortality

Short name:

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sodium channel modulation

Graphical Representation

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Click to download graphical representation template

Authors

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Kellie Fay

Point of Contact

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Kellie Fay   (email point of contact)

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 Do not cite 1.29 Under Development


This AOP was last modified on January 27, 2018 15:34

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Revision dates for related pages

Page Revision Date/Time
modulation, sodium channel September 16, 2017 10:15
prolonged, Depolarization of neuronal membrane September 16, 2017 10:15
Overactivation, Neuronotransmitter release September 16, 2017 10:15
Overactivation, muscle contraction September 16, 2017 10:15
Increased, Ataxia, paralysis, or hyperactivity September 16, 2017 10:15
Increased, Mortality May 15, 2017 11:34
modulation, sodium channel leads to prolonged, Depolarization of neuronal membrane December 03, 2016 16:37
prolonged, Depolarization of neuronal membrane leads to Overactivation, Neuronotransmitter release December 03, 2016 16:37
Overactivation, Neuronotransmitter release leads to Overactivation, muscle contraction December 03, 2016 16:37
Overactivation, muscle contraction leads to Increased, Ataxia, paralysis, or hyperactivity December 03, 2016 16:37
Increased, Ataxia, paralysis, or hyperactivity leads to Increased, Mortality December 03, 2016 16:37

Abstract

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The voltage-gated sodium channels present on neuronal axons are the primary molecular target of pyrethroid insecticides. These chemicals selectively bind open sodium channels, allowing continuous entry of sodium ions into the cell. This hyperdepolarization of the nerve membrane results in a prolonged tail current, uncontrolled firing and neurotransmitter release. Ultimately, ataxia, paralysis and death result.


Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 598 modulation, sodium channel modulation, sodium channel
2 KE 599 prolonged, Depolarization of neuronal membrane prolonged, Depolarization of neuronal membrane
3 KE 600 Overactivation, Neuronotransmitter release Overactivation, Neuronotransmitter release
4 KE 601 Overactivation, muscle contraction Overactivation, muscle contraction
5 KE 602 Increased, Ataxia, paralysis, or hyperactivity Increased, Ataxia, paralysis, or hyperactivity
6 AO 351 Increased, Mortality Increased, Mortality

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
modulation, sodium channel leads to prolonged, Depolarization of neuronal membrane adjacent
prolonged, Depolarization of neuronal membrane leads to Overactivation, Neuronotransmitter release adjacent
Overactivation, muscle contraction leads to Increased, Ataxia, paralysis, or hyperactivity adjacent
Increased, Ataxia, paralysis, or hyperactivity leads to Increased, Mortality adjacent
Overactivation, Neuronotransmitter release leads to Overactivation, muscle contraction non-adjacent

Network View

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Stressors

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Life Stage Applicability

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Life stage Evidence
During development and at adulthood

Taxonomic Applicability

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Term Scientific Term Evidence Link
insects insects NCBI
fish fish NCBI

Sex Applicability

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Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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