ArticlePloS one2015
Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- Common genetic variants of the cardiac sodium channel alter patient response to class 1b antiarrhythmics.Journal of precision medicine (Amsterdam, Netherlands) · 2026Article
- Plant-derived compounds as potential candidates for atrial fibrillation drug discovery: A review on phytochemicals with atrial-selective activity.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Common Genetic Variants of The Cardiac Sodium Channel Alter Patient Response to Class 1b Antiarrhythmics.bioRxiv : the preprint server for biology · 2026Article
- Pharmacological targeting and characterization of Voltage-Gated Sodium Channels (VGSCs) expressed in the high-grade glioma microenvironment.BMC cancer · 2025Article
- Evaluation of a New Riluzole-Based Compound VA945 on Sodium and Potassium Conductances Expressed by SH-SY5Y- Derived Neurons.Journal of neurochemistry · 2025Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Intra-channel bi-epitopic crosslinking unleashes ultrapotent antibodies targeting NaCell reports. Medicine · 2024Article
- Natural Compounds Purified from the Leaves ofInternational journal of molecular sciences · 2023Article
- Protein 14-3-3 Influences the Response of the Cardiac Sodium Channel NaThe Journal of pharmacology and experimental therapeutics · 2023Article
- A Review of the Therapeutic Targeting of SCN9A and Nav1.7 for Pain Relief in Current Human Clinical Trials.Journal of pain research · 2023Review
- Molecular Modeling of Cardiac Sodium Channel with Mexiletine.Membranes · 2022Article
- Sodium Channels and Local Anesthetics-Old Friends With New Perspectives.Frontiers in pharmacology · 2022Review
- Effects of Mexiletine on a Race-specific Mutation in NaFrontiers in physiology · 2022Article
- Highly Parallelized, Multicolor Optogenetic Recordings of Cellular Activity for Therapeutic Discovery Applications in Ion Channels and Disease-Associated Excitable Cells.Frontiers in molecular neuroscience · 2022Article
- Bioisosteric Modification of To042: Synthesis and Evaluation of Promising Use-Dependent Inhibitors of Voltage-Gated Sodium Channels.ChemMedChem · 2021Article
- Pharmacological Inhibition of the Voltage-Gated Sodium Channel NaACS pharmacology & translational science · 2021Article
- Inhibition of Nav1.7 channel by a novel blocker QLS-81 for alleviation of neuropathic pain.Acta pharmacologica Sinica · 2021Article
- Lacosamide Inhibition of NaFrontiers in pharmacology · 2021Article
- Block of Voltage-Gated Sodium Channels by Atomoxetine in a State- and Use-dependent Manner.Frontiers in pharmacology · 2021Article
- Human neuronal signaling and communication assays to assess functional neurotoxicity.Archives of toxicology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that are considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias and relief of pain. To gain mechanistic insights into action of anti-arrhythmics, we characterized biophysical properties of Nav1.5 and Nav1.7 channels stably expressed in HEK293 cells and compared their use-dependent block in response to mexiletine and lidocaine using whole-cell patch clamp recordings. While the voltage-dependent activation of Nav1.5 or Nav1.7 was not affected by mexiletine and lidocaine, the steady-state fast and slow inactivation of Nav1.5 and Nav1.7 were significantly shifted to hyperpolarized direction by either mexiletine or lidocaine in dose-dependent manner. Both mexiletine and lidocaine enhanced the slow component of closed-state inactivation, with mexiletine exerting stronger inhibition on either Nav1.5 or Nav1.7. The recovery from inactivation of Nav1.5 or Nav1.7 was significantly prolonged by mexiletine compared to lidocaine. Furthermore, mexiletine displayed a pronounced and prominent use-dependent inhibition of Nav1.5 than lidocaine, but not Nav1.7 channels. Taken together, our findings demonstrate differential responses to blockade by mexiletine and lidocaine that preferentially affect the gating of Nav1.5, as compared to Nav1.7; and mexiletine exhibits stronger use-dependent block of Nav1.5. The differential gating properties of Nav1.5 and Nav1.7 in response to mexiletine and lidocaine may help explain the drug effectiveness and advance in new designs of safe and specific sodium channel blockers for treatment of cardiac arrhythmia or pain.
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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.