ArticleCardiovascular research2014
Tubulin polymerization disrupts cardiac β-adrenergic regulation of late INa.
Article in Cardiovascular research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Obstructive Sleep Apnea and Arrhythmia: A Narrative Review of Arrhythmogenic Mechanisms.Diagnostics (Basel, Switzerland) · 2026Review
- Nanoscale organization in the cell membrane dynamically modulates the biophysics of voltage-gated sodium channels.Nature communications · 2026Article
- Computational and experimental identification of putative αTAT1 modulators: implications for nervous system function.Frontiers in pharmacology · 2025Article
- NaInternational journal of molecular sciences · 2024Article
- Modulation of fast sodium current in airway smooth muscle cells by exchange protein directly activated by cAMP.American journal of physiology. Cell physiology · 2024Article
- Molecular and Functional Relevance of NaInternational journal of molecular sciences · 2023Article
- CaMKII-Dependent Contractile Dysfunction and Pro-Arrhythmic Activity in a Mouse Model of Obstructive Sleep Apnea.Antioxidants (Basel, Switzerland) · 2023Article
- Pharmacological inhibition of SK-channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events.Journal of cardiovascular electrophysiology · 2023Article
- Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer.Cancers · 2021Article
- Enhanced Heart Failure in Redox-Dead Cys17Ser PKARIα Knock-In Mice.Journal of the American Heart Association · 2021Article
- Cellular Mechanisms of the Anti-Arrhythmic Effect of Cardiac PDE2 Overexpression.International journal of molecular sciences · 2021Article
- Loss of CASK Accelerates Heart Failure Development.Circulation research · 2021Article
- Review
- Article
- Exchange protein activated by cyclic-adenosine monophosphate (Epac) regulates atrial fibroblast function and controls cardiac remodelling.Cardiovascular research · 2019Article
- β-adrenergic regulation of late NaJournal of molecular and cellular cardiology · 2018Article
- Late sodium current inhibitors to treat exercise-induced obstruction in hypertrophic cardiomyopathy: an in vitro study in human myocardium.British journal of pharmacology · 2018Article
- Distribution of cardiac sodium channels in clusters potentiates ephaptic interactions in the intercalated disc.The Journal of physiology · 2018Article
- Arrhythmogenic Mechanisms in Heart Failure: Linking β-Adrenergic Stimulation, Stretch, and Calcium.Frontiers in physiology · 2018Review
- Early effects of Epac depend on the fine-tuning of the sarcoplasmic reticulum CaJournal of molecular and cellular cardiology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
aimsThe anticancer drug paclitaxel (TXL) that polymerizes microtubules is associated with arrhythmias and sinus node dysfunction. TXL can alter membrane expression of Na channels (NaV1.5) and Na current (INa), but the mechanisms are unknown. Calcium/calmodulin-dependent protein kinase II (CaMKII) can be activated by β-adrenergic stimulation and regulates INa gating. We tested whether TXL interferes with isoproterenol (ISO)-induced activation of CaMKII and consequent INa regulation. METHODS AND
resultsIn wild-type mouse myocytes, the addition of ISO (1 µmol/L) resulted in increased CaMKII auto-phosphorylation (western blotting). This increase was completely abolished after pre-treatment with TXL (100 µmol/L, 1.5 h). The mechanism was further investigated in human embryonic kidney cells. TXL inhibited the ISO-induced β-arrestin translocation. Interestingly, both knockdown of β-arrestin2 expression using small interfering RNA and inhibition of exchange protein directly activated by cAMP (Epac) blocked the ISO-induced CaMKII auto-phosphorylation similar to TXL. The generation of cAMP, however, was unaltered (Epac1-camps). CaMKII-dependent Na channel function was measured using patch-clamp technique in isolated cardiomyoctes. ISO stimulation failed to induce CaMKII-dependent enhancement of late INa and Na channel inactivation (negative voltage shift in steady-state activation and enhanced intermediate inactivation) after pre-incubation with TXL. Consistent with this, TXL also inhibited ISO-induced CaMKII-specific Na channel phosphorylation (at serine 571 of NaV1.5).
conclusionPre-incubation with TXL disrupts the ISO-dependent CaMKII activation and consequent Na channel regulation. This may be important for patients receiving TXL treatments, but also relevant for conditions of increased CaMKII expression and enhanced β-adrenergic stimulation like in heart failure.
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