Key Event Title
|Level of Biological Organization|
Key Event Components
|sodium channel inhibitor activity||sodium channel protein type 1 subunit alpha||decreased|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP|
|sodium channel modulation||MolecularInitiatingEvent|
Key Event Description
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
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.
Domain of Applicability
Evidence for Perturbation by Stressor
Overview for Molecular Initiating Event
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.