Key Event Overview
Please follow link to widget page to edit this section.
If you manually enter text in this section, it will get automatically altered or deleted in subsequent edits using the widgets.
AOPs Including This Key Event
|AOP Name||Event Type||Essentiality|
|Axonal sodium channel modulation leading to acute mortality||MIE|
The following are chemical initiators that operate directly through this Event:
Level of Biological Organization
How this Key Event works
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.
Evidence Supporting Taxonomic Applicability
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.