期刊
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 66, 期 -, 页码 88-95出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ibmb.2015.09.011
关键词
Sodium channel blocker insecticides; Sodium channel; Insecticide resistance; Local anesthetics
资金
- National Institutes of Health [GM057440]
- Ministry of Agriculture of China [201203038]
- Ministry of Education of China [B07030]
- China Scholar Council
Indoxacarb and metaflumizone are two sodium channel blocker insecticides (SCBIs). They preferably bind to and trap sodium channels in the slow-inactivated non-conducting state, a mode of action similar to that of local anesthetics (LAs). Recently, two sodium channel mutations, F1845Y ((FY)-Y-4i15) and V1848I ((VI)-I-4i18), in the transmembrane segment 6 of domain IV (IVS6), were identified to be associated with indoxacarb resistance in Plutella xylostella. F-4i15 is. known to be critical for the action of LAs on mammalian sodium channels. Previously, mutation F(4i15)A in a cockroach sodium channel, BgNa(v)1-1a, has been shown to reduce the action. of lidocaine, a LA, but not the action of SCBIs. In this study, we introduced mutations (FY)-Y-4i15 and V(4i18)A/I individually into the cockroach sodium channel, BgNa(v)1-1a, and conducted functional analysis of the three mutants in Xenopus oocytes. We found that both the (FY)-Y-4i15 and (VI)-I-4i18 mutations reduced the inhibition of sodium current by indoxacarb, DCJW (an active metabolite of indoxacarb) and metaflumizone. (FY)-Y-4i15 and (VI)-I-4i18 mutations also reduced the use-dependent block of sodium current by lidocaine. In contrast, substitution V(4i18)A enhanced the action metaflumizone and lidocaine. These results show that both (FY)-Y-4i15 and (VI)-I-4i18 mutations may contribute to target-site resistance to SCBIs, and provide the first molecular evidence for common amino acid determinants on insect sodium channels involved in action of SCBIs and LA. (C) 2015 Elsevier Ltd. All rights reserved.
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