Voltage-gated sodium channels are the major targets of several classes of insecticides, including pyrethroids. However, sensitivities of many insect pest species to pyrethroids have gradually decreased due to overuse in pest management programs. One major mechanism of pyrethroid resistance known as knockdown resistance (kdr) involves mutations in the sodium channel gene. Three new mutations in helix IIIS6 of sodium channel (I1532T and F1534S/L) are recently detected in several pyrethroid-resistant populations of Aedes albopictus. The roles of these mutations in pyrethroid resistance have not been functionally examined. We introduced mutations I1532T and F1534S/L alone or in combination into the pyrethroid-sensitive sodium channel AaNav1-1 from Aedes aegypti by site-directed mutagenesis and explored effects of these mutations on the channel gating and sensitivity to pyrethroids. No significant modifications in channel properties were detected, except for a slightly changed activation by F1534S and I1532T + F1534S. However, I1532T and F1534S/L substantially reduced the channel sensitivity to Type I pyrethroids, permethrin and bifenthrin, but not to two Type II pyrethroids, deltamethrin and cypermethrin. The double mutations did not increase the channel resistance to permethrin or bifenthrin. We have built a Nav1.4-based homology model of the AaNav1-1 channel and docked pyrethroids in the model to explain different sensitivities of the mutants to Type I and Type II pyrethroids. The results will assist in developing molecular markers for monitoring pest resistance to pyrethroids. They also provide new insight in the molecular basis of different action of Type I and Type II pyrethroids on sodium channels.
Keywords: Homology modeling; Knockdown resistance; Ligand docking; Sodium channel; Type I pyrethroids; TypeII pyrethroids.
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