title: 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.
abstract: 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.
authors.affiliation: Department of Entomology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Yuzhe
authors.initials: Y
authors.lastname: Du
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Liu
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Nomura
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Khambay
authors.forename: Ke
authors.initials: K
authors.lastname: Dong
mesh_terms: D000409:Alanine / Q000235:genetics* / Q000502:physiology; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D003058:Cockroaches / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009570:Nitriles / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011722:Pyrethrins / Q000494:pharmacology*; D016415:Sequence Alignment; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*
chemical_list: D019476:Insect Proteins; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C017180:decamethrin; D000409:Alanine