ArticleThe Journal of physiology2011
Shaping a new Ca²⁺ conductance to suppress early afterdepolarizations in cardiac myocytes.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
- Are physiological oscillations physiological?The Journal of physiology · 2026Review
- Nanobody-thioesterase chimeras to specifically target protein palmitoylation.Nature communications · 2025Article
- The C-terminus of Rad is required for membrane localization and L-type calcium channel regulation.The Journal of general physiology · 2024Article
- Impact of Combined Modulation of Two Potassium Ion Currents on Spiral Waves and Turbulent States in the Heart.Entropy (Basel, Switzerland) · 2024Article
- S-acylation of Ca2+ transport proteins: molecular basis and functional consequences.Biochemical Society transactions · 2024Review
- Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Cardiac Alternans: From Bedside to Bench and Back.Circulation research · 2023Review
- Biological noise is a key determinant of the reproducibility and adaptability of cardiac pacemaking and EC coupling.The Journal of general physiology · 2022Review
- Suppression of ventricular arrhythmias by targeting late L-type Ca2+ current.The Journal of general physiology · 2021Article
- Prediction of arrhythmia susceptibility through mathematical modeling and machine learning.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- L-type channel inactivation balances the increased peak calcium current due to absence of Rad in cardiomyocytes.The Journal of general physiology · 2021Article
- Circadian Rhythms of Early Afterdepolarizations and Ventricular Arrhythmias in a Cardiomyocyte Model.Biophysical journal · 2021Article
- Canard analysis reveals why a large Ca2+ window current promotes early afterdepolarizations in cardiac myocytes.PLoS computational biology · 2020Article
- Arrhythmogenic late CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Dynamic clamping human and rabbit atrial calcium current: narrowing IThe Journal of physiology · 2019Article
- Multiple Dynamical Mechanisms of Phase-2 Early Afterdepolarizations in a Human Ventricular Myocyte Model:Frontiers in physiology · 2019Article
- Illuminating cell signaling with genetically encoded FRET biosensors in adult mouse cardiomyocytes.The Journal of general physiology · 2018Article
- Determinants of early afterdepolarization properties in ventricular myocyte models.PLoS computational biology · 2018Article
- Wanted: Class VI Antiarrhythmic Drug Action; New Start for a Rational Drug Therapy.Journal of heart health · 2018Article
- Exclusion of alternative exon 33 of CaProceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Sudden cardiac death (SCD) due to ventricular fibrillation (VF) is a major world-wide health problem. A common trigger of VF involves abnormal repolarization of the cardiac action potential causing early afterdepolarizations (EADs). Here we used a hybrid biological-computational approach to investigate the dependence of EADs on the biophysical properties of the L-type Ca(2+) current (I(Ca,L)) and to explore how modifications of these properties could be designed to suppress EADs. EADs were induced in isolated rabbit ventricular myocytes by exposure to 600 μmol l(-1) H(2)O(2) (oxidative stress) or lowering the external [K(+)] from 5.4 to 2.0-2.7 mmol l(-1) (hypokalaemia). The role of I(Ca,L) in EAD formation was directly assessed using the dynamic clamp technique: the paced myocyte's V(m) was input to a myocyte model with tunable biophysical parameters, which computed a virtual I(Ca,L), which was injected into the myocyte in real time. This virtual current replaced the endogenous I(Ca,L), which was suppressed with nifedipine. Injecting a current with the biophysical properties of the native I(Ca,L) restored EAD occurrence in myocytes challenged by H(2)O(2) or hypokalaemia. A mere 5 mV depolarizing shift in the voltage dependence of activation or a hyperpolarizing shift in the steady-state inactivation curve completely abolished EADs in myocytes while maintaining a normal Ca(i) transient. We propose that modifying the biophysical properties of I(Ca,L) has potential as a powerful therapeutic strategy for suppressing EADs and EAD-mediated arrhythmias.
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