ArticleThe Journal of biological chemistry2013
Proton sensors in the pore domain of the cardiac voltage-gated sodium channel.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Blocking the voltage-gated sodium channel hNaFEBS open bio · 2025Article
- Impact of Impaired Kidney Function on Arrhythmia-Promoting Cardiac Ion Channel Regulation.International journal of molecular sciences · 2023Review
- A new polymodal gating model of the proton-activated chloride channel.PLoS biology · 2023Article
- Late Sodium Current of the Heart: Where Do We Stand and Where Are We Going?Pharmaceuticals (Basel, Switzerland) · 2022Review
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Investigation ofFrontiers in molecular neuroscience · 2022Article
- pH-Channeling in Cancer: How pH-Dependence of Cation Channels Shapes Cancer Pathophysiology.Cancers · 2020Review
- Late Sodium Current Inhibitors as Potential Antiarrhythmic Agents.Frontiers in pharmacology · 2020Review
- Cationic Modulation of Voltage-Gated Sodium Channel (Nav1.5): Neonatal Versus Adult Splice Variants-1. Monovalent (HBioelectricity · 2019Article
- A Mixed Periodic Paralysis & Myotonia Mutant, P1158S, Imparts pH-Sensitivity in Skeletal Muscle Voltage-gated Sodium Channels.Scientific reports · 2018Article
- Effects of acidosis on neuronal voltage-gated sodium channels: Nav1.1 and Nav1.3.Channels (Austin, Tex.) · 2018Article
- Mechanisms and models of cardiac sodium channel inactivation.Channels (Austin, Tex.) · 2017Review
- Depolarization of the conductance-voltage relationship in the NaV1.5 mutant, E1784K, is due to altered fast inactivation.PloS one · 2017Article
- Extracellular protons inhibit charge immobilization in the cardiac voltage-gated sodium channel.Biophysical journal · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protons impart isoform-specific modulation of inactivation in neuronal, skeletal muscle, and cardiac voltage-gated sodium (Na(V)) channels. Although the structural basis of proton block in Na(V) channels has been well described, the amino acid residues responsible for the changes in Na(V) kinetics during extracellular acidosis are as yet unknown. We expressed wild-type (WT) and two pore mutant constructs (H880Q and C373F) of the human cardiac Na(V) channel, Na(V)1.5, in Xenopus oocytes. C373F and H880Q both attenuated proton block, abolished proton modulation of use-dependent inactivation, and altered pH modulation of the steady-state and kinetic parameters of slow inactivation. Additionally, C373F significantly reduced the maximum probability of use-dependent inactivation and slow inactivation, relative to WT. H880Q also significantly reduced the maximum probability of slow inactivation and shifted the voltage dependence of activation and fast inactivation to more positive potentials, relative to WT. These data suggest that Cys-373 and His-880 in Na(V)1.5 are proton sensors for use-dependent and slow inactivation and have implications in isoform-specific modulation of Na(V) channels.
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