ArticleThe Journal of general physiology2012
Scorpion β-toxin interference with NaV channel voltage sensor gives rise to excitatory and depressant modes.
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 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Exceptionally selective voltage-sensor trapping of NaScientific reports · 2026Article
- Beta Toxins Isolated from the ScorpionToxins · 2025Article
- Article
- Article
- Deciphering Scorpion Toxin-Induced Pain: Molecular Mechanisms and Ion Channel Dynamics.International journal of biological sciences · 2025Review
- Scorpion Peptides and Ion Channels: An Insightful Review of Mechanisms and Drug Development.Toxins · 2023Review
- Extracellular hemin is a reverse use-dependent gating modifier of cardiac voltage-gated NaBiological chemistry · 2022Article
- Pharmacological Dissection of the Crosstalk between NaInternational journal of molecular sciences · 2022Article
- New Challenges Resulting From the Loss of Function of NaFrontiers in pharmacology · 2021Review
- Structural and Functional Analyses of Cone Snail Toxins.Marine drugs · 2019Review
- Review
- Subtype Specificity of β-Toxin Tf1a fromToxins · 2018Article
- Article
- The envenomation of general physiology throughout the last century.The Journal of general physiology · 2017Review
- The hitchhiker's guide to the voltage-gated sodium channel galaxy.The Journal of general physiology · 2016Review
- From foe to friend: using animal toxins to investigate ion channel function.Journal of molecular biology · 2015Review
- Article
- Animal toxins influence voltage-gated sodium channel function.Handbook of experimental pharmacology · 2014Review
- Opening the shaker K+ channel with hanatoxin.The Journal of general physiology · 2013Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Scorpion β toxins, peptides of ∼70 residues, specifically target voltage-gated sodium (Na(V)) channels to cause use-dependent subthreshold channel openings via a voltage-sensor trapping mechanism. This excitatory action is often overlaid by a not yet understood depressant mode in which Na(V) channel activity is inhibited. Here, we analyzed these two modes of gating modification by β-toxin Tz1 from Tityus zulianus on heterologously expressed Na(V)1.4 and Na(V)1.5 channels using the whole cell patch-clamp method. Tz1 facilitated the opening of Na(V)1.4 in a use-dependent manner and inhibited channel opening with a reversed use dependence. In contrast, the opening of Na(V)1.5 was exclusively inhibited without noticeable use dependence. Using chimeras of Na(V)1.4 and Na(V)1.5 channels, we demonstrated that gating modification by Tz1 depends on the specific structure of the voltage sensor in domain 2. Although residue G658 in Na(V)1.4 promotes the use-dependent transitions between Tz1 modification phenotypes, the equivalent residue in Na(V)1.5, N803, abolishes them. Gating charge neutralizations in the Na(V)1.4 domain 2 voltage sensor identified arginine residues at positions 663 and 669 as crucial for the outward and inward movement of this sensor, respectively. Our data support a model in which Tz1 can stabilize two conformations of the domain 2 voltage sensor: a preactivated outward position leading to Na(V) channels that open at subthreshold potentials, and a deactivated inward position preventing channels from opening. The results are best explained by a two-state voltage-sensor trapping model in that bound scorpion β toxin slows the activation as well as the deactivation kinetics of the voltage sensor in domain 2.
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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.