ArticleBiophysical journal2000
Residues in Na(+) channel D3-S6 segment modulate both batrachotoxin and local anesthetic affinities.
Article in Biophysical journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 105 citations in OpenAlex.
- Batrachotoxin-sensitive sodium channels in toxic birds challenge "target mutation" strategy of toxin autoresistance.iScience · 2026Article
- Article
- Dual receptor-sites reveal the structural basis for hyperactivation of sodium channels by poison-dart toxin batrachotoxin.Nature communications · 2024Article
- Historical Perspective of the Characterization of Conotoxins Targeting Voltage-Gated Sodium Channels.Marine drugs · 2023Review
- Differential effects of modified batrachotoxins on voltage-gated sodium channel fast and slow inactivation.Cell chemical biology · 2022Article
- Differences in local anaesthetic and antiepileptic binding in the inactivated state of human sodium channel Nav1.4.Biophysical journal · 2021Article
- Hydrophobic Drug/Toxin Binding Sites in Voltage-Dependent KFrontiers in pharmacology · 2020Review
- Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.The Journal of general physiology · 2017Article
- Inhibition of Sodium Ion Channel Function with Truncated Forms of Batrachotoxin.ACS chemical neuroscience · 2016Article
- The hitchhiker's guide to the voltage-gated sodium channel galaxy.The Journal of general physiology · 2016Review
- Mutations in the transmembrane helix S6 of domain IV confer cockroach sodium channel resistance to sodium channel blocker insecticides and local anesthetics.Insect biochemistry and molecular biology · 2015Article
- State-dependent inter-repeat contacts of exceptionally conserved asparagines in the inner helices of sodium and calcium channels.Pflugers Archiv : European journal of physiology · 2015Article
- Folding similarity of the outer pore region in prokaryotic and eukaryotic sodium channels revealed by docking of conotoxins GIIIA, PIIIA, and KIIIA in a NavAb-based model of Nav1.4.The Journal of general physiology · 2014Article
- Animal toxins influence voltage-gated sodium channel function.Handbook of experimental pharmacology · 2014Review
- Molecular Insights into the Local Anesthetic Receptor within Voltage-Gated Sodium Channels Using Hydroxylated Analogs of Mexiletine.Frontiers in pharmacology · 2012Article
- Lidocaine reduces the transition to slow inactivation in Na(v)1.7 voltage-gated sodium channels.British journal of pharmacology · 2011Article
- Identification of new batrachotoxin-sensing residues in segment IIIS6 of the sodium channel.The Journal of biological chemistry · 2011Article
- Analysis of the action of lidocaine on insect sodium channels.Insect biochemistry and molecular biology · 2011Article
- Neurotoxins and their binding areas on voltage-gated sodium channels.Frontiers in pharmacology · 2011Article
- Molecular mechanism of allosteric modification of voltage-dependent sodium channels by local anesthetics.The Journal of general physiology · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Batrachotoxin (BTX) alters the gating of voltage-gated Na(+) channels and causes these channels to open persistently, whereas local anesthetics (LAs) block Na(+) conductance. The BTX and LA receptors have been mapped to several common residues in D1-S6 and D4-S6 segments of the Na(+) channel alpha-subunit. We substituted individual residues with lysine in homologous segment D3-S6 of the rat muscle mu1 Na(+) channel from F1274 to N1281 to determine whether additional residues are involved in BTX and LA binding. Two mutant channels, mu1-S1276K and mu1-L1280K, when expressed in mammalian cells, become completely resistant to 5 microM BTX during repetitive pulses. The activation and/or fast inactivation gating of these mutants is substantially different from that of wild type. These mutants also display approximately 10-20-fold reduction in bupivacaine affinity toward their inactivated state but show only approximately twofold affinity changes toward their resting state. These results demonstrate that residues mu1-S1276 and mu1-L1280 in D3-S6 are critical for both BTX and LA binding interactions. We propose that LAs interact readily with these residues from D3-S6 along with those from D1-S6 and D4-S6 in close proximity when the Na(+) channel is in its inactivated state. Implications of this state-dependent binding model for the S6 alignment are discussed.
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.