ArticleThe Journal of general physiology2012
Use-dependent block of the voltage-gated Na(+) channel by tetrodotoxin and saxitoxin: effect of pore mutations that change ionic selectivity.
Article in The Journal of general physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Efficacy of sodium channel blockers in treating myotonia is independent of action potential sodium current block.The Journal of physiology · 2026Article
- Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel.Medicinal research reviews · 2024Review
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Therapeutic targeting of voltage-gated sodium channel NaFrontiers in pharmacology · 2024Review
- Computational Investigation of Selected Spike Protein Mutations in SARS-CoV-2: Delta, Omicron, and Some Circulating Subvariants.Pathogens (Basel, Switzerland) · 2023Article
- Trifunctional Saxitoxin Conjugates for Covalent Labeling of Voltage-Gated Sodium Channels.Chembiochem : a European journal of chemical biology · 2023Article
- Voltage-Gated Sodium Channel NaCancers · 2023Article
- In Silico Analysis of Tetrodotoxin Binding in Voltage-Gated Sodium Ion Channels from Toxin-Resistant Animal Lineages.Marine drugs · 2022Article
- Article
- Local Anesthetic Like Inhibition of the Cardiac NaJournal of experimental pharmacology · 2022Article
- Pharmacological determination of the fractional block of Nav channels required to impair neuronal excitability andFrontiers in cellular neuroscience · 2022Article
- Challenges and Opportunities for Therapeutics Targeting the Voltage-Gated Sodium Channel Isoform NaJournal of medicinal chemistry · 2019Review
- Review
- The envenomation of general physiology throughout the last century.The Journal of general physiology · 2017Review
- Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods.EFSA journal. European Food Safety Authority · 2017Article
- Characterization of Endogenous Sodium Channels in the ND7-23 Neuroblastoma Cell Line: Implications for Use as a Heterologous Ion Channel Expression System Suitable for Automated Patch Clamp Screening.Assay and drug development technologies · 2016Article
- Saxitoxin Modulates Immunological Parameters and Gene Transcription in Mytilus chilensis Hemocytes.International journal of molecular sciences · 2015Article
- A disulfide tether stabilizes the block of sodium channels by the conotoxin μO§-GVIIJ.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Voltage-gated Na(+) channels (NaV channels) are specifically blocked by guanidinium toxins such as tetrodotoxin (TTX) and saxitoxin (STX) with nanomolar to micromolar affinity depending on key amino acid substitutions in the outer vestibule of the channel that vary with NaV gene isoforms. All NaV channels that have been studied exhibit a use-dependent enhancement of TTX/STX affinity when the channel is stimulated with brief repetitive voltage depolarizations from a hyperpolarized starting voltage. Two models have been proposed to explain the mechanism of TTX/STX use dependence: a conformational mechanism and a trapped ion mechanism. In this study, we used selectivity filter mutations (K1237R, K1237A, and K1237H) of the rat muscle NaV1.4 channel that are known to alter ionic selectivity and Ca(2+) permeability to test the trapped ion mechanism, which attributes use-dependent enhancement of toxin affinity to electrostatic repulsion between the bound toxin and Ca(2+) or Na(+) ions trapped inside the channel vestibule in the closed state. Our results indicate that TTX/STX use dependence is not relieved by mutations that enhance Ca(2+) permeability, suggesting that ion-toxin repulsion is not the primary factor that determines use dependence. Evidence now favors the idea that TTX/STX use dependence arises from conformational coupling of the voltage sensor domain or domains with residues in the toxin-binding site that are also involved in slow inactivation.
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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.