Cover Image


View/Hide Left Panel


One unintended consequence of the liberal and worldwide use of dichlorodiphenyltrichloroethane, pyrethrin, and pyrethroid insecticides has been the rapid, massively parallel evolution of resistance to these pesticides in insects (Taylor et al., 1993; Liu et al., 2000; Davies et al., 2007; Jones et al., 2012). Starting with their use in the 1940s, the first indications of resistance, so-called knockdown resistance because insects were no longer knocked down by normal concentrations of the insecticide, were evident in the early 1950s. These insecticides target the Nav1 channels of insects. They cross the cell membrane and lodge in a hydrophobic pocket in the inner mouth of the channel, where they are believed to prevent the inactivation gate (domain III–IV linker) from occluding the inner mouth of the channel. This allows Na+ ions to continue flowing into the cell, causing hyperexcitabiity. Amino acid substitutions have been discovered in a variety of insects at a number of sites in the inner mouth of the insect Nav channel (para in Drosophila) that either reduce pesticide binding or alter the channel properties to counteract the effects of insecticides. An example of the latter is a substitution that causes the channel to open at more positive potentials and to enhance the rate at which Nav channels enter closed-state inactivation. This minimizes the number of open channels counteracting the prolonged channel opening caused by insecticides.

The rapid evolution of Nav channels in insects exposed to insecticides is one of many warnings we have about the robust abilities of insect pests to overcome our best attempts to wipe them out.


Like many key components of the nervous system, Nav channels existed before neurons. It is likely that the Nav channels of choanoflagellates and early metazoans were permeable to both Na+ and Ca2+ and evolved enhanced selectivity to Na+ in parallel in early bilaterians and jellyfish. Although it is convenient to think that invertebrates possess only a single Nav1 channel gene, it is worth scouring the wealth of new genomes to determine whether there are any lineage-specific duplications, and if so, what this might mean. Further, we have little information on the Nav2 channels of invertebrates.

The parallel expansion of Nav channel genes in tetrapods and teleosts occurred along with an increase in the number of telencephalic nuclei in both groups. This was coincident with or just after the great Devonian extinction, during which teleosts began their domination of the aquatic and tetrapods of the terrestrial habitats. More types of Nav channels may allow for more sophisticated computational possibilities and energy savings.

The National Academies of Sciences, Engineering, and Medicine
500 Fifth St. N.W. | Washington, D.C. 20001

Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement