Metaflumizone inhibits the honeybee NaV 1 channel by targeting recovery from slow inactivation

FEBS Lett. 2017 Dec;591(23):3842-3849. doi: 10.1002/1873-3468.12897. Epub 2017 Nov 12.

Abstract

Metaflumizone is the latest addition to the armamentarium of the Na+ channel inhibitor insecticide family. We used the Xenopus oocyte expression system and a Markovian model to assess the effect of metaflumizone on Apis mellifera Na+ channels (AmNaV 1). Our results reveal that metaflumizone inhibits AmNaV 1 channels by targeting the kinetics of recovery from slow inactivation. Multistate modeling of fast and slow inactivation of the AmNaV 1 channel made it possible to study the effects of metaflumizone on a set of rate constants underlying the transition between the open and inactivated conformations and provided insights into their specificity. We conclude that the methods we used could be extended to assessing the toxicity of other Na+ channel inhibitor insecticides.

Keywords: AmNaV1; NaV; insecticides; metaflumizone; voltage-gated Na+ channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bees / genetics
  • Bees / metabolism*
  • Female
  • In Vitro Techniques
  • Insect Proteins / antagonists & inhibitors*
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Insecticide Resistance
  • Insecticides / pharmacology*
  • Kinetics
  • Models, Biological
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Semicarbazones / pharmacology*
  • Voltage-Gated Sodium Channel Blockers / pharmacology*
  • Voltage-Gated Sodium Channels / genetics
  • Voltage-Gated Sodium Channels / metabolism*
  • Xenopus

Substances

  • Insect Proteins
  • Insecticides
  • Recombinant Proteins
  • Semicarbazones
  • Voltage-Gated Sodium Channel Blockers
  • Voltage-Gated Sodium Channels
  • metaflumizone