Functional analysis of a rat sodium channel carrying a mutation for insect knock-down resistance (kdr) to pyrethroids

Pyrethroid insensitivity in resistant (kdr) insects has been correlated with a leucine to phenylalanine replacement in the S6 transmembrane segment of domain II of the axonal sodium channel alpha(para)-subunit. An alpha-subunit of rat brain type II sodium channel containing this mutation has been expressed and its sensitivity to permethrin compared with that of the wild-type channel. The steady-state activation curve of the mutant was shifted 14 mV in the depolarizing direction. We propose that an equivalent shift of the sodium current activation curve in kdr insects could account for their low sensitivity to permethrin toxicity.