ArticleProceedings of the National Academy of Sciences of the United States of America2012
Marked difference in saxitoxin and tetrodotoxin affinity for the human nociceptive voltage-gated sodium channel (Nav1.7) [corrected].
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
44 citing papers in PubMed.
- A designer saxitoxin-engineered sodium channel pair as a general tool for subtype-selective inhibition.Cell chemical biology · 2026Article
- Review
- Molecular determinant of low-voltage dependence of human NaNature communications · 2026Article
- Amide-Linked Local Anesthetics Alter Tumor Biology in a Complex Human Tissue Model of Non-Small Cell Lung Adenocarcinoma.Advanced biology · 2025Article
- Article
- Saxitoxin: A Comprehensive Review of Its History, Structure, Toxicology, Biosynthesis, Detection, and Preventive Implications.Marine drugs · 2025Review
- A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers.eLife · 2025Article
- Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins.Nature communications · 2025Article
- A structural atlas of druggable sites on NaChannels (Austin, Tex.) · 2024Review
- Evolution of ion channels in cetaceans: a natural experiment in the tree of life.Scientific reports · 2024Article
- Review
- Discovery of Selective Inhibitors of NaACS medicinal chemistry letters · 2022Article
- Current Trends and New Challenges in Marine Phycotoxins.Marine drugs · 2022Review
- Novel Local Anesthetics in Clinical Practice: Pharmacologic Considerations and Potential Roles for the Future.Anesthesiology and pain medicine · 2022Review
- Towards Structure-Guided Development of Pain Therapeutics Targeting Voltage-Gated Sodium Channels.Frontiers in pharmacology · 2022Review
- The contribution of ion channels to shaping macrophage behaviour.Frontiers in pharmacology · 2022Review
- Sodium Channels and Local Anesthetics-Old Friends With New Perspectives.Frontiers in pharmacology · 2022Review
- Reviewing Interspecies Interactions as a Driving Force Affecting the Community Structure in Lakes via Cyanotoxins.Microorganisms · 2021Review
- Chemoenzymatic Total Synthesis of Natural Products.Accounts of chemical research · 2021Review
- Discovery of a selective, state-independent inhibitor of NaScientific reports · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
Human nociceptive voltage-gated sodium channel (Na(v)1.7), a target of significant interest for the development of antinociceptive agents, is blocked by low nanomolar concentrations of (-)-tetrodotoxin(TTX) but not (+)-saxitoxin (STX) and (+)-gonyautoxin-III (GTX-III). These findings question the long-accepted view that the 1.7 isoform is both tetrodotoxin- and saxitoxin-sensitive and identify the outer pore region of the channel as a possible target for the design of Na(v)1.7-selective inhibitors. Single- and double-point amino acid mutagenesis studies along with whole-cell electrophysiology recordings establish two domain III residues (T1398 and I1399), which occur as methionine and aspartate in other Na(v) isoforms, as critical determinants of STX and gonyautoxin-III binding affinity. An advanced homology model of the Na(v) pore region is used to provide a structural rationalization for these surprising results.
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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.