Electrophysiological identification of site‐insensitive mechanisms in knockdown‐resistant strains (kdr, super‐kdr) of the housefly larva (Musca domestica)

Abstract

AbstractThe effects of pyrethroids were studied upon isolated segmental nerves and neuromuscular junctions in both susceptible (Cooper) and knockdown‐resistant (kdr; super‐kdr) strains of housefly larvae (Musca domestica L.). Isolated segmental nerves contained neither cell bodies nor synaptic contacts; thus, any effects of pyrethroids were attributed solely to their actions upon voltage‐dependent Na+ channels. Threshold concentrations of the type II pyrethroid, deltamethrin, required to elevate the spontaneous firing rate of these nerves were determined. Both resistant strains were about ten times less sensitive to deltamethrin than the susceptible strain, but insensitivity of super‐kdr nerves was no greater than in the less resistant kdr strain. At neuromuscular junctions, the minimum concentrations of pyrethroids needed to trigger massive increases in the frequency of miniature excitatory postsynaptic potentials (mEPSPs) were determined for deltamethrin and the type I pyrethroid, fenfluthrin. With fenfluthrin there was no detectable difference between the junctions of kdr and super‐kdr strains, which were both about ten‐fold less sensitive than Cooper junctions. With deltamethrin, kdr junctions were about 30 times less sensitive than those of Cooper; super‐kdr junctions were dramatically insensitive to deltamethrin, being some 10000‐ and 300‐fold less sensitive than those of Cooper and kdr respectively. Thus, in the synaptic assay, super‐kdr conferred an extension in resistance over kdr only against the type II pyrethroid, it being ineffective against fenfluthrin. We suggest that kdr resistance comprises at least two site‐insensitive areas within the nervous system. One involves insensitivity of the Na+ channel and has similar efficacy in both kdr and super‐kdr strains against type I and II pyrethroids; the other is associated with the presynaptic terminal and is particularly effective in super‐kdr resistance against type II pyrethroids. The latter could be associated with Ca2+‐activated phosphorylation of proteins involved with neurotransmitter release. Such phosphorylation reactions are known to be perturbed by pyrethroids, especially by type II compounds.