ArticleFrontiers in pharmacology2013
Proton-dependent inhibition of the cardiac sodium channel Nav1.5 by ranolazine.
Article in Frontiers in pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- 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
- Blocking the voltage-gated sodium channel hNaFEBS open bio · 2025Article
- Recent Advances in Computer-Aided Structure-Based Drug Design on Ion Channels.International journal of molecular sciences · 2023Review
- Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization.Circulation · 2023Article
- Article
- Cannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity.The Journal of general physiology · 2021Article
- J Point and ST Elevation Resembling Brugada: A Marker of Mortality in Methanol Toxicity.Cardiology research and practice · 2021Article
- Cationic Modulation of Voltage-Gated Sodium Channel (Nav1.5): Neonatal Versus Adult Splice Variants-1. Monovalent (HBioelectricity · 2019Article
- The efficacy of Ranolazine on E1784K is altered by temperature and calcium.Scientific reports · 2018Article
- Inhibitory effects of hesperetin on Nav1.5 channels stably expressed in HEK 293 cells and on the voltage-gated cardiac sodium current in human atrial myocytes.Acta pharmacologica Sinica · 2016Article
- Electrophysiological Characteristics of the LQT2 Syndrome MutationFrontiers in physiology · 2016Article
- Mechanisms of sudden cardiac death: oxidants and metabolism.Circulation research · 2015Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ranolazine is clinically approved for treatment of angina pectoris and is a potential candidate for antiarrhythmic, antiepileptic, and analgesic applications. These therapeutic effects of ranolazine hinge on its ability to inhibit persistent or late Na(+) currents in a variety of voltage-gated sodium channels. Extracellular acidosis, typical of ischemic events, may alter the efficiency of drug/channel interactions. In this study, we examined pH modulation of ranolazine's interaction with the cardiac sodium channel, Nav1.5. We performed whole-cell path clamp experiments at extracellular pH 7.4 and 6.0 on Nav1.5 transiently expressed in HEK293 cell line. Consistent with previous studies, we found that ranolazine induced a stable conformational state in the cardiac sodium channel with onset/recovery kinetics and voltage-dependence resembling intrinsic slow inactivation. This interaction diminished the availability of the channels in a voltage- and use-dependent manner. Low extracellular pH impaired inactivation states leading to an increase in late Na(+) currents. Ranolazine interaction with the channel was also slowed 4-5 fold. However, ranolazine restored the voltage-dependent steady-state availability profile, thereby reducing window/persistent currents at pH 6.0 in a manner comparable to pH 7.4. These results suggest that ranolazine is effective at therapeutically relevant concentrations (10 μM), in acidic extracellular pH, where it compensates for impaired native slow inactivation.
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