An important role of a pyrethroid-sensing residue F1519 in the action of the N-alkylamide insecticide BTG 502 on the cockroach sodium channel

作者：Du Yuzhe; Khambay Bhupinder; Dong Ke^*

来源：Insect Biochemistry and Molecular Biology, 2011, 41(7): 446-450.

DOI：10.1016/j.ibmb.2011.03.005

• BTG 502
• Batrachotoxin
• Pyrethroids
• Sodium channel
• Knockdown resistance
• Site-directed mutagenesis

Deltamethrin, a pyrethroid insecticide, and BIG 502, an alkylamide insecticide, target voltage-gated sodium channels. Deltamethrin binds to a unique receptor site and causes prolonged opening of sodium channels by inhibiting deactivation and inactivation. Previous (22)Na(+) influx and receptor binding assays using mouse brain synaptoneurosomes showed that BIG 502 antagonized the binding and action of batrachotoxin (BTX), a site 2 sodium channel neurotoxin. However, the effect of BIG 502 has not been examined directly on sodium channels expressed in Xenopus oocytes. In this study, we examined the effect of BIG 502 on wild-type and mutant cockroach sodium channels expressed in Xenopus oocytes. Toxin competition experiments confirmed that BIG 502 antagonizes the action of BTX and possibly shares a common receptor site with BTX. However, unlike BTX which causes persistent activation of sodium channels, BIG 502 reduces the amplitude of peak sodium current. A previous study showed that BIG 502 was more toxic to pyrethroid-resistant house flies possessing a super-kdr (knockdown resistance) mechanism than to pyrethroid-susceptible house flies. However, we found that the cockroach sodium channels carrying the equivalent super-kdr mutations (M918T and L1014F) were not more sensitive to BIG 502 than the wild-type channel. Instead, a kdr mutation, F1519I, which reduces pyrethroid binding, abolished the action of BIG 502. These results provide evidence the actions of alkylamide and pyrethroid insecticides require a common sodium channel residue.

• 出版日期2011-7