Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels.
Tan J
,
Liu Z
,
Nomura Y
,
Goldin AL
,
Dong K
.
???displayArticle.abstract???
Alternative splicing is a major mechanism by which potassium and calcium channels increase functional diversity in animals. Extensive alternative splicing of the para sodium channel gene and developmental regulation of alternative splicing have been reported in Drosophila species. Alternative splicing has also been observed for several mammalian voltage-gated sodium channel genes. However, the functional significance of alternative splicing of sodium channels has not been demonstrated. In this study, we identified three mutually exclusive alternative exons encoding part of segments 3 and 4 of domain III in the German cockroach sodium channel gene, para(CSMA). The splice site is conserved in the mouse, fish, and human Na(v)1.6 sodium channel genes, suggesting an ancient origin. One of the alternative exons possesses a stop codon, which would generate a truncated protein with only the first two domains. The splicing variant containing the stop codon is detected only in the PNS, whereas the other two full-size variants were detected in both the PNS and CNS. When expressed in Xenopus oocytes, the two splicing variants produced robust sodium currents, but with different gating properties, whereas the splicing variant with the stop codon did not produce any detectable sodium current. Furthermore, these two functional splicing variants exhibited a striking difference in sensitivity to a pyrethroid insecticide, deltamethrin. Exon swapping partially reversed the channel sensitivity to deltamethrin. Our results therefore provide the first evidence that alternative splicing of a sodium channel gene produces pharmacologically distinct channels.
Belcher,
Cloning of a sodium channel alpha subunit from rabbit Schwann cells.
1995, Pubmed
Belcher,
Cloning of a sodium channel alpha subunit from rabbit Schwann cells.
1995,
Pubmed
Bourinet,
Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels.
1999,
Pubmed
,
Xenbase
Byerly,
Ionic currents of Drosophila neurons in embryonic cultures.
1988,
Pubmed
Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
Pubmed
Dietrich,
Functional analysis of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia.
1998,
Pubmed
,
Xenbase
Dong,
A single amino acid change in the para sodium channel protein is associated with knockdown-resistance (kdr) to pyrethroid insecticides in German cockroach.
1997,
Pubmed
Dong,
Linkage of kdr-type resistance and the para-homologous sodium channel gene in German cockroaches (Blattella germanica).
1994,
Pubmed
Feng,
Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function.
1995,
Pubmed
,
Xenbase
Ginsburg,
Differential sensitivity of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels to the insecticide allethrin in rat dorsal root ganglion neurons.
1993,
Pubmed
Goldin,
Diversity of mammalian voltage-gated sodium channels.
1999,
Pubmed
Goldin,
Maintenance of Xenopus laevis and oocyte injection.
1992,
Pubmed
,
Xenbase
Goldin,
Resurgence of sodium channel research.
2001,
Pubmed
Gustafson,
Mutually exclusive exon splicing of type III brain sodium channel alpha subunit RNA generates developmentally regulated isoforms in rat brain.
1993,
Pubmed
Hanrahan,
RNA editing of the Drosophila para Na(+) channel transcript. Evolutionary conservation and developmental regulation.
2000,
Pubmed
Hockerman,
Molecular determinants of drug binding and action on L-type calcium channels.
1997,
Pubmed
Ingles,
Characterization of voltage-sensitive sodium channel gene coding sequences from insecticide-susceptible and knockdown-resistant house fly strains.
1996,
Pubmed
Iverson,
A-type potassium channels expressed from Shaker locus cDNA.
1988,
Pubmed
,
Xenbase
Kontis,
Site-directed mutagenesis of the putative pore region of the rat IIA sodium channel.
1993,
Pubmed
,
Xenbase
Lagrutta,
Functional differences among alternatively spliced variants of Slowpoke, a Drosophila calcium-activated potassium channel.
1994,
Pubmed
Lee,
The V410M mutation associated with pyrethroid resistance in Heliothis virescens reduces the pyrethroid sensitivity of house fly sodium channels expressed in Xenopus oocytes.
2001,
Pubmed
,
Xenbase
Lin,
Alternative splicing of a short cassette exon in alpha1B generates functionally distinct N-type calcium channels in central and peripheral neurons.
1999,
Pubmed
,
Xenbase
Lin,
Identification of functionally distinct isoforms of the N-type Ca2+ channel in rat sympathetic ganglia and brain.
1997,
Pubmed
,
Xenbase
Linford,
Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel.
1998,
Pubmed
Liu,
Alternative splicing of the BSC1 gene generates tissue-specific isoforms in the German cockroach.
2001,
Pubmed
Liu,
Synergistic interaction between two cockroach sodium channel mutations and a tobacco budworm sodium channel mutation in reducing channel sensitivity to a pyrethroid insecticide.
2002,
Pubmed
Loughney,
Molecular analysis of the para locus, a sodium channel gene in Drosophila.
1989,
Pubmed
Malouf,
A two-motif isoform of the major calcium channel subunit in skeletal muscle.
1992,
Pubmed
Mount,
Splicing signals in Drosophila: intron size, information content, and consensus sequences.
1992,
Pubmed
O'Dowd,
Sodium current density correlates with expression of specific alternatively spliced sodium channel mRNAs in single neurons.
1995,
Pubmed
Plummer,
Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells.
1997,
Pubmed
Reenan,
The mle(napts) RNA helicase mutation in drosophila results in a splicing catastrophe of the para Na+ channel transcript in a region of RNA editing.
2000,
Pubmed
Saito,
Expression of ion channels and mutational effects in giant Drosophila neurons differentiated from cell division-arrested embryonic neuroblasts.
1991,
Pubmed
Salkoff,
Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila.
1987,
Pubmed
Sarao,
Developmentally regulated alternative RNA splicing of rat brain sodium channel mRNAs.
1991,
Pubmed
Schaller,
Alternatively spliced sodium channel transcripts in brain and muscle.
1992,
Pubmed
Smith,
The L1014F point mutation in the house fly Vssc1 sodium channel confers knockdown resistance to pyrethroids.
1997,
Pubmed
,
Xenbase
Smith,
Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in xenopus oocytes.
1998,
Pubmed
,
Xenbase
Smith,
Functional analysis of the mouse Scn8a sodium channel.
1998,
Pubmed
,
Xenbase
Soderlund,
Differential sensitivity of sodium channel isoforms and sequence variants to pyrethroid insecticides.
2000,
Pubmed
,
Xenbase
Song,
Differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant single sodium channels.
1996,
Pubmed
Tabarean,
Potent modulation of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels by the type II pyrethroid deltamethrin.
1998,
Pubmed
Tan,
Novel sodium channel gene mutations in Blattella germanica reduce the sensitivity of expressed channels to deltamethrin.
2002,
Pubmed
,
Xenbase
Tatebayashi,
Differential mechanism of action of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels.
1994,
Pubmed
Thackeray,
Developmentally regulated alternative splicing generates a complex array of Drosophila para sodium channel isoforms.
1994,
Pubmed
Thackeray,
Conserved alternative splicing patterns and splicing signals in the Drosophila sodium channel gene para.
1995,
Pubmed
Timpe,
Four cDNA clones from the Shaker locus of Drosophila induce kinetically distinct A-type potassium currents in Xenopus oocytes.
1988,
Pubmed
,
Xenbase
Vais,
Activation of Drosophila sodium channels promotes modification by deltamethrin. Reductions in affinity caused by knock-down resistance mutations.
2000,
Pubmed
,
Xenbase
Vais,
Functional analysis of a rat sodium channel carrying a mutation for insect knock-down resistance (kdr) to pyrethroids.
1997,
Pubmed
,
Xenbase
Wang,
A phenylalanine residue at segment D3-S6 in Nav1.4 voltage-gated Na(+) channels is critical for pyrethroid action.
2001,
Pubmed
Warmke,
Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology.
1997,
Pubmed
,
Xenbase
Zhao,
Functional and evolutionary consequences of pyrethroid resistance mutations in S6 transmembrane segments of a voltage-gated sodium channel.
2000,
Pubmed
,
Xenbase
