API

Event: 598

Key Event Title

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modulation, sodium channel

Short name

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modulation, sodium channel

Key Event Component

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Process Object Action
sodium channel inhibitor activity sodium channel protein type 1 subunit alpha decreased

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
Axonal sodium channel modulation leading to acute mortality MolecularInitiatingEvent

Stressors

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Level of Biological Organization

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Biological Organization
Molecular

Cell term

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Cell term
eukaryotic cell


Organ term

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Taxonomic Applicability

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Life Stages

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Sex Applicability

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How This Key Event Works

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Voltage-gated sodium channels present on neuronal axons open and close by the action of two largely independent gates which operate oppositely according to membrane potential(see Hodgkin-Huxley model; Hodgkin and Huxley, 1952). Pyrethroids primarily act to delay the closing of the sodium channel activation gate (Vijverberg et al., 1982).


How It Is Measured or Detected

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Changes in nerve membrane permeability and kinetic properties of ionic channels can be studied using the voltage clamp or patch clamp technique. Pyrethroid action resulting in prolonged opening of the voltage-gated sodium ion channel is evidenced by the prolonged sodium tail current and subsequent repetitive nerve impulses. The Novascreen assay, NVS_IC_rNaCh_site2, detects sodium channel 1A receptor binding.


Evidence Supporting Taxonomic Applicability

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Evidence for Perturbation by Stressor


Overview for Molecular Initiating Event

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References

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Hodgkin, A. L., & AF Huxley, (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. The Journal of Physiology, 117(4), 500–544.

Vijverberg, HPM, JM Van der Zalm, J Van der Bercken (1982). Similar mode of action of pyrethroids and DDT on sodium channel gaiting in myelinated nerves. Nature, 295 (5850), 601-603.