ArticlePLoS computational biology2018
A model for cooperative gating of L-type Ca2+ channels and its effects on cardiac alternans dynamics.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
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- The pathophysiological role of MiRNAs in heart failure.Frontiers in cardiovascular medicine · 2026Review
- Multiscale stochastic modeling for calcium dynamics in cardiac electrophysiology: assessing whole-cell model reliability under phosphorylation and LCC downregulation.Frontiers in network physiology · 2026Article
- The mechanism of electrical remodeling in atrial fibrillation and current research status of natural drugs and active ingredients inhibiting atrial electrical remodeling.Frontiers in cardiovascular medicine · 2026Review
- Role of dynamical instability in QT interval variability and early afterdepolarization propensity.Biophysical journal · 2025Article
- Bend it like BIN1: how a membrane-curving adaptor protein shapes cardiac physiology.American journal of physiology. Heart and circulatory physiology · 2025Review
- Dynamical effects of mechano-chemo-transduction on cardiac alternans.Biophysical journal · 2025Article
- The impact of dynamic reversal potential on the evolution of action potential attributes during spike trains.Frontiers in computational neuroscience · 2025Article
- Enhancing myocardial function with cardiac contractility modulation: potential and challenges.ESC heart failure · 2024Review
- CaJournal of molecular and cellular cardiology · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Harnessing conserved signaling and metabolic pathways to enhance the maturation of functional engineered tissues.NPJ Regenerative medicine · 2022Review
- Mechanisms and physiological implications of cooperative gating of clustered ion channels.Physiological reviews · 2022Review
- Mechanisms and Regulation of Cardiac CaInternational journal of molecular sciences · 2021Review
- Biventricular Pulsus Alternans in a Dog with Pulmonic Stenosis and Sepsis.CASE (Philadelphia, Pa.) · 2021Article
- Absence of Rgs5 Influences the Spatial and Temporal Fluctuation of Cardiac Repolarization in Mice.Frontiers in physiology · 2021Article
- Modulation of CaChannels (Austin, Tex.) · 2020Article
- Human iPSC modelling of a familial form of atrial fibrillation reveals a gain of function of If and ICaL in patient-derived cardiomyocytes.Cardiovascular research · 2020Article
- Clusters of cooperative ion channels enable a membrane-potential-based mechanism for short-term memory.eLife · 2020Article
- Arrhythmogenic late CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In ventricular myocytes, membrane depolarization during the action potential (AP) causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which trigger the release of calcium (Ca2+) from the sarcoplasmic reticulum (SR). This results in an increase in intracellular Ca2+ (Cai) that initiates contraction. During pulsus alternans, cardiac contraction is unstable, going from weak to strong in successive beats despite a constant heart rate. These cardiac alternans can be caused by the instability of membrane potential (Vm) due to steep AP duration (APD) restitution (Vm-driven alternans), instability of Cai cycling (Ca2+-driven alternans), or both, and may be modulated by functional coupling between clustered CaV1.2 (e.g. cooperative gating). Here, mathematical analysis and computational models were used to determine how changes in the strength of cooperative gating between LTCCs may impact membrane voltage and intracellular Ca2+ dynamics in the heart. We found that increasing the degree of coupling between LTCCs increases the amplitude of Ca2+ currents (ICaL) and prolongs AP duration (APD). Increased AP duration is known to promote cardiac alternans, a potentially arrhythmogenic substrate. In addition, our analysis shows that increasing the strength of cooperative activation of LTCCs makes the coupling of Ca2+ on the membrane voltage (Cai→Vm coupling) more positive and destabilizes the Vm-Cai dynamics for Vm-driven alternans and Cai-driven alternans, but not for quasiperiodic oscillation. These results suggest that cooperative gating of LTCCs may have a major impact on cardiac excitation-contraction coupling, not only by prolonging APD, but also by altering Cai→Vm coupling and potentially promoting cardiac arrhythmias.
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Registered trials
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