ArticleNature communications2011
Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels.
Article in Nature communications, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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The trial behind it
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Who cites it
62 citing papers in PubMed.
- Late IMedicinal research reviews · 2026Review
- Chemical tuning reveals a cation-π gating bridge between the voltage-sensor and pore domains in the KProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multiscale computational analysis reveals enhanced allosteric modulation of Nav1.5 by dual binding of dapagliflozin and ertugliflozin.Scientific reports · 2025Article
- Differential Inhibition by Cenobamate of Canonical Human Nav1.5 Ion Channels and Several Point Mutants.International journal of molecular sciences · 2025Article
- Inhibition of NMDA receptors and other ion channel types by membrane-associated drugs.Frontiers in pharmacology · 2025Review
- Flecainide Specifically Targets the Monovalent Countercurrent Through the Cardiac Ryanodine Receptor, While a Dominant Opposing CaInternational journal of molecular sciences · 2024Article
- Inhibitory Effects of Cenobamate on Multiple Human Cardiac Ion Channels and Possible Arrhythmogenic Consequences.Biomolecules · 2024Article
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Structural basis for inhibition of the cardiac sodium channel by the atypical antiarrhythmic drug ranolazine.Nature cardiovascular research · 2023Article
- Protein 14-3-3 Influences the Response of the Cardiac Sodium Channel NaThe Journal of pharmacology and experimental therapeutics · 2023Article
- Tuning phenylalanine fluorination to assess aromatic contributions to protein function and stability in cells.Nature communications · 2023Article
- Block of Voltage-Gated Sodium Channels by Aripiprazole in a State-Dependent Manner.International journal of molecular sciences · 2022Article
- Role of a conserved ion-binding site tyrosine in ion selectivity of the Na+/K+ pump.The Journal of general physiology · 2022Article
- Common Structural Pattern for Flecainide Binding in Atrial-Selective KPharmaceutics · 2022Article
- Structure-guided unlocking of NaNature communications · 2022Article
- Druggability of Voltage-Gated Sodium Channels-Exploring Old and New Drug Receptor Sites.Frontiers in pharmacology · 2022Review
- The Bradycardic Agent Ivabradine Acts as an Atypical Inhibitor of Voltage-Gated Sodium Channels.Frontiers in pharmacology · 2022Article
- Late sodium current and calcium homeostasis in arrhythmogenesis.Channels (Austin, Tex.) · 2021Review
- Article
- Structural modeling of NaBiophysics reports · 2021Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Cardiac sodium channels are established therapeutic targets for the management of inherited and acquired arrhythmias by class I anti-arrhythmic drugs (AADs). These drugs share a common target receptor bearing two highly conserved aromatic side chains, and are subdivided by the Vaughan-Williams classification system into classes Ia-c based on their distinct effects on the electrocardiogram. How can these drugs elicit distinct effects on the cardiac action potential by binding to a common receptor? Here we use fluorinated phenylalanine derivatives to test whether the electronegative surface potential of aromatic side chains contributes to inhibition by six class I AADs. Surprisingly, we find that class Ib AADs bind via a strong electrostatic cation-pi interaction, whereas class Ia and Ic AADs rely significantly less on this interaction. Our data shed new light on drug-target interactions underlying the inhibition of cardiac sodium channels by clinically relevant drugs and provide information for the directed design of AADs.
Indexed as
Identifiers
21673672What 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.