ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 150 citations in OpenAlex.
- Mutations M918T, M918L, and L1014F impair pyrethroid binding and alter gating of the Megalurothrips usitatus sodium channel.Pest management science · 2026Article
- Synthetic pyrethroid resistance in Haematobia irritans subsp. exigua (Diptera: Muscidae): knockdown-recovery observed, a new putative resistance-linked mutation detected, and a complete voltage-gated sodium channel gene transcript sequenced.Journal of economic entomology · 2026Article
- Structural insights into insect-selective sodium channel toxins drive AI-enhanced biopesticide design.Nature communications · 2026Article
- Butterfly brains change in morphology and in gene splicing patterns after brief pheromone exposure.BMC biology · 2026Article
- Impact of Aedes aegypti V1016I and F1534C knockdown resistance genotypes on operational interventions.Scientific reports · 2025Article
- A unique mechanism of transfluthrin action revealed by mapping its binding sites in the mosquito sodium channel.Insect biochemistry and molecular biology · 2024Article
- Origins and Evolution of Human Tandem Duplicated Exon Substitution Events.Genome biology and evolution · 2022Article
- Characterization of two kdr mutations at predicted pyrethroid receptor site 2 in the sodium channels of Aedes aegypti and Nilaparvata lugens.Insect biochemistry and molecular biology · 2022Article
- Charge substitutions at the voltage-sensing module of domain III enhance actions of site-3 and site-4 toxins on an insect sodium channel.Insect biochemistry and molecular biology · 2021Article
- Mapping the interaction surface of scorpion β-toxins with an insect sodium channel.The Biochemical journal · 2021Article
- Distinct functional properties of sodium channel variants are associated with usage of alternative exons in Nilaparvata lugens.Insect biochemistry and molecular biology · 2020Article
- Article
- Purification and Characterization of a Novel Insecticidal Toxin, μ-sparatoxin-Hv2, from the Venom of the SpiderToxins · 2018Article
- The NaFrontiers in pharmacology · 2018Review
- Alanine to valine substitutions in the pore helix IIIP1 and linker-helix IIIL45 confer cockroach sodium channel resistance to DDT and pyrethroids.Neurotoxicology · 2017Article
- Mutations of two acidic residues at the cytoplasmic end of segment IIIS6 of an insect sodium channel have distinct effects on pyrethroid resistance.Insect biochemistry and molecular biology · 2017Article
- Molecular Characterization of Voltage-Gated Sodium Channels and Their Relations with Paralytic Shellfish Toxin Bioaccumulation in the Pacific Oyster Crassostrea gigas.Marine drugs · 2017Article
- Diversity and frequency of kdr mutations within Anopheles sinensis populations from Guangxi, China.Malaria journal · 2016Article
- Article
- Regulation of membrane excitability: a convergence on voltage-gated sodium conductance.Molecular neurobiology · 2015Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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.
Indexed as
Identifiers
12097481PMC3062512W2137932146What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.