| 16431283 |
Du Y, Liu Z, Nomura Y, Khambay B, Dong K: An alanine in segment 3 of domain III (IIIS3) of the cockroach sodium channel contributes to the low pyrethroid sensitivity of an alternative splice variant. Insect Biochem Mol Biol. 2006 Feb;36(2):161-8. Epub 2005 Dec 20.
In a previous study, we showed that two alternative exons (G1 and G2 encoding IIIS3-S4) were involved in the differential sensitivity of two cockroach sodium channel splice variants, BgNa (v) 1-1 and BgNa (v) 2-1 (previously called KD1 and KD2), to deltamethrin, a pyrethroid insecticide (Tan, et al., 2002b. Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels. J. Neurosci. 22, 5300-5309.). Here, we report the identification of an amino acid residue in exon G2 that contributes to the low deltamethrin sensitivity of BgNa (v) 2-1. Replacement of A1356 in BgNa (v) 2-1 with the corresponding V1356 in BgNa (v) 1-1 enhanced the sensitivity of the BgNa (v) 2-1 channel to deltamethrin by six-fold. Conversely, substitution of V1356 with A1356 in BgNa (v) 1-1 produced a recombinant BgNa (v) 1-1 channel that was 5-fold more resistant to deltamethrin. These results demonstrate that A1356 contributes to the low sensitivity of BgNa (v) 2-1 to deltamethrin. A1356V substitution also shifted the voltage-dependence of activation by 10 mV in the hyperpolarizing direction. Possible mechanisms by which this amino acid change affects the action of pyrethroids on the sodium channel are discussed. |
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