ArticleBiochemistry2010
Cell membrane expression of cardiac sodium channel Na(v)1.5 is modulated by alpha-actinin-2 interaction.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- SCN5A Cardiomyopathy: from Ion Channel Dysfunction To Clinical Disease.Current cardiology reports · 2025Review
- A transcriptional enhancer regulates cardiac maturation.Nature cardiovascular research · 2024Article
- Maturation of iPSC-derived cardiomyocytes in a heart-on-a-chip device enables modeling of dilated cardiomyopathy caused by R222Q-SCN5A mutation.Biomaterials · 2023Article
- Regulated cell death pathways in cardiomyopathy.Acta pharmacologica Sinica · 2023Review
- Rupture of Splenic Artery Aneurysm in Patient with ACTN2 Mutation.Journal of clinical medicine · 2023Article
- Microtubule plus-end tracking proteins: novel modulators of cardiac sodium channels and arrhythmogenesis.Cardiovascular research · 2023Article
- Small-conductance calcium-activated potassium channels in the heart: expression, regulation and pathological implications.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Novel ACTN2 missense variant is associated with idiopathic ventricular fibrillation: a case report.European heart journal. Case reports · 2022Article
- Minor hypertrophic cardiomyopathy genes, major insights into the genetics of cardiomyopathies.Nature reviews. Cardiology · 2022Review
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Mono- and Biallelic Protein-Truncating Variants in Alpha-Actinin 2 Cause Cardiomyopathy Through Distinct Mechanisms.Circulation. Genomic and precision medicine · 2021Article
- Phosphorylation of Lamin A/C at serine 22 modulates NaPhysiological reports · 2021Article
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- Phosphorylation of cardiac voltage-gated sodium channel: Potential players with multiple dimensions.Acta physiologica (Oxford, England) · 2019Review
- Article
- A Distinct Pool of NaFrontiers in physiology · 2019Article
- Sarcomeric and nonmuscle α-actinin isoforms exhibit differential dynamics at skeletal muscle Z-lines.Cytoskeleton (Hoboken, N.J.) · 2018Article
- Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology.Circulation. Genomic and precision medicine · 2018Article
- Changes in cardiac Nav1.5 expression, function, and acetylation by pan-histone deacetylase inhibitors.American journal of physiology. Heart and circulatory physiology · 2016Article
- Physiological and Pathophysiological Insights of Nav1.4 and Nav1.5 Comparison.Frontiers in pharmacology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Cardiac sodium channel Na(v)1.5 plays a critical role in heart excitability and conduction. The molecular mechanism that underlies the expression of Na(v)1.5 at the cell membrane is poorly understood. Previous studies demonstrated that cytoskeleton proteins can be involved in the regulation of cell surface expression and localization of several ion channels. We performed a yeast two-hybrid screen to identify Na(v)1.5-associated proteins that may be involved in channel function and expression. We identified alpha-actinin-2 as an interacting partner of the cytoplasmic loop connecting domains III and IV of Na(v)1.5 (Na(v)1.5/LIII-IV). Co-immunoprecipitation and His(6) pull-down assays confirmed the physical association between Na(v)1.5 and alpha-actinin-2 and showed that the spectrin-like repeat domain is essential for binding of alpha-actinin-2 to Na(v)1.5. Patch-clamp studies revealed that the interaction with alpha-actinin-2 increases sodium channel density without changing their gating properties. Consistent with these findings, coexpression of alpha-actinin-2 and Na(v)1.5 in tsA201 cells led to an increase in the level of expression of Na(v)1.5 at the cell membrane as determined by cell surface biotinylation. Lastly, immunostaining experiments showed that alpha-actinin-2 was colocalized with Na(v)1.5 along the Z-lines and in the plasma membrane. Our data suggest that alpha-actinin-2, which is known to regulate the functional expression of the potassium channels, may play a role in anchoring Na(v)1.5 to the membrane by connecting the channel to the actin cytoskeleton network.
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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.