ArticleThe Journal of biological chemistry2011
Identification of new batrachotoxin-sensing residues in segment IIIS6 of the sodium channel.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Batrachotoxin-sensitive sodium channels in toxic birds challenge "target mutation" strategy of toxin autoresistance.iScience · 2026Article
- Article
- Peptide toxins that target vertebrate voltage-gated sodium channels underly the painful stings of harvester ants.The Journal of biological chemistry · 2024Article
- Screening an In-House Isoquinoline Alkaloids Library for New Blockers of Voltage-Gated NaMolecules (Basel, Switzerland) · 2022Article
- Differential effects of modified batrachotoxins on voltage-gated sodium channel fast and slow inactivation.Cell chemical biology · 2022Article
- Article
- How do batrachotoxin-bearing frogs and birds avoid self intoxication?The Journal of general physiology · 2021Article
- Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on "toxin sponge" proteins.The Journal of general physiology · 2021Article
- Antiepileptic Drug Tiagabine Does Not Directly Target Key Cardiac Ion Channels Kv11.1, Nav1.5 and Cav1.2.Molecules (Basel, Switzerland) · 2021Article
- KInternational journal of molecular sciences · 2020Review
- Synthesis of chiral 1,4-oxazepane-5-carboxylic acids from polymer-supported homoserine.RSC advances · 2020Article
- Hydrophobic Drug/Toxin Binding Sites in Voltage-Dependent KFrontiers in pharmacology · 2020Review
- Batrachotoxin acts as a stent to hold open homotetrameric prokaryotic voltage-gated sodium channels.The Journal of general physiology · 2019Article
- Atomic Mechanisms of Timothy Syndrome-Associated Mutations in Calcium Channel Cav1.2.Frontiers in physiology · 2019Article
- Predicting Structural Details of the Sodium Channel Pore Basing on Animal Toxin Studies.Frontiers in pharmacology · 2018Review
- Article
- Molecular basis of selective resistance of the bumblebee BiNaProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Single rat muscle NaProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Inhibition of Sodium Ion Channel Function with Truncated Forms of Batrachotoxin.ACS chemical neuroscience · 2016Article
- The Receptor Site and Mechanism of Action of Sodium Channel Blocker Insecticides.The Journal of biological chemistry · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Ion permeation through voltage-gated sodium channels is modulated by various drugs and toxins. The atomistic mechanisms of action of many toxins are poorly understood. A steroidal alkaloid batrachotoxin (BTX) causes persistent channel activation by inhibiting inactivation and shifting the voltage dependence of activation to more negative potentials. Traditionally, BTX is considered to bind at the channel-lipid interface and allosterically modulate the ion permeation. However, amino acid residues critical for BTX action are found in the inner helices of all four repeats, suggesting that BTX binds in the pore. In the octapeptide segment IFGSFFTL in IIIS6 of a cockroach sodium channel BgNa(V), besides Ser_3i15 and Leu_3i19, which correspond to known BTX-sensing residues of mammalian sodium channels, we found that Gly_3i14 and Phe_3i16 are critical for BTX action. Using these data along with published data as distance constraints, we docked BTX in the Kv1.2-based homology model of the open BgNa(V) channel. We arrived at a model in which BTX adopts a horseshoe conformation with the horseshoe plane normal to the pore axis. The BTX ammonium group is engaged in cation-π interactions with Phe_3i16 and BTX moieties interact with known BTX-sensing residues in all four repeats. Oxygen atoms at the horseshoe inner surface constitute a transient binding site for permeating cations, whereas the bulky BTX molecule would resist the pore closure, thus causing persistent channel activation. Our study reinforces the concept that steroidal sodium channel agonists bind in the inner pore of sodium channels and elaborates the atomistic mechanism of BTX action.
Indexed as
Identifiers
What 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.