ArticleAmerican journal of physiology. Heart and circulatory physiology2008
Alternans of cardiac calcium cycling in a cluster of ryanodine receptors: a simulation study.
Article in American journal of physiology. Heart and circulatory physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Cardiac Alternans: From Bedside to Bench and Back.Circulation research · 2023Review
- Modeling Calcium Cycling in the Heart: Progress, Pitfalls, and Challenges.Biomolecules · 2022Review
- Voltage-mediated mechanism for calcium wave synchronization and arrhythmogenesis in atrial tissue.Biophysical journal · 2022Article
- Optical Ultrastructure of Large Mammalian Hearts Recovers Discordant Alternans byFrontiers in network physiology · 2022Article
- Cardiac Alternans Occurs through the Synergy of Voltage- and Calcium-Dependent Mechanisms.Membranes · 2021Article
- Cx43 hemichannel microdomain signaling at the intercalated disc enhances cardiac excitability.The Journal of clinical investigation · 2021Article
- Electrophysiological Mechanisms Underlying T-Wave Alternans and Their Role in Arrhythmogenesis.Frontiers in physiology · 2021Review
- Delayed global feedback in the genesis and stability of spatiotemporal excitation patterns in paced biological excitable media.PLoS computational biology · 2020Article
- Mechanistic insight into spontaneous transition from cellular alternans to arrhythmia-A simulation study.PLoS computational biology · 2018Article
- Mechanisms linking T-wave alternans to spontaneous initiation of ventricular arrhythmias in rabbit models of long QT syndrome.The Journal of physiology · 2018Article
- Mechanism for Triggered Waves in Atrial Myocytes.Biophysical journal · 2017Article
- Alternans in atria: Mechanisms and clinical relevance.Medicina (Kaunas, Lithuania) · 2017Review
- Studying dyadic structure-function relationships: a review of current modeling approaches and new insights into CaClinical Medicine Insights. Cardiology · 2017Article
- On the Adjacency Matrix of RyR2 Cluster Structures.PLoS computational biology · 2015Article
- Cardiac myocyte alternans in intact heart: Influence of cell-cell coupling and β-adrenergic stimulation.Journal of molecular and cellular cardiology · 2015Article
- The mechanisms of calcium cycling and action potential dynamics in cardiac alternans.Circulation research · 2015Article
- T-tubule disruption promotes calcium alternans in failing ventricular myocytes: mechanistic insights from computational modeling.Journal of molecular and cellular cardiology · 2015Article
- Superresolution modeling of calcium release in the heart.Biophysical journal · 2014Article
- Nonlinear and Stochastic Dynamics in the Heart.Physics reports · 2014Article
- Cardiac alternans and ventricular fibrillation: a bad case of ryanodine receptors reneging on their duty.Circulation research · 2014Article
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Authors and funding
6 authors.
Funding
Abstract
Mechanical alternans in cardiac muscle is associated with intracellular Ca(2+) alternans. Mechanisms underlying intracellular Ca(2+) alternans are unclear. In previous experimental studies, we produced alternans of systolic Ca(2+) under voltage clamp, either by partially inhibiting the Ca(2+) release mechanism, or by applying small depolarizing pulses. In each case, alternans relied on propagating waves of Ca(2+) release. The aim of this study is to investigate by computer modeling how alternans of systolic Ca(2+) is produced. A mathematical model of a cardiac cell with 75 coupled elements is developed, with each element contains L-type Ca(2+) current, a subspace into which Ca release takes place, a cytoplasmic space, sarcoplasmic reticulum (SR) release channels [ryanodine receptor (RyR)], and uptake sites (SERCA). Interelement coupling is via Ca(2+) diffusion between neighboring subspaces via cytoplasmic spaces and network SR spaces. Small depolarizing pulses were simulated by step changes of cell membrane potential (20 mV) with random block of L-type channels. Partial inhibition of the release mechanism is mimicked by applying a reduction of RyR open probability in response to full stimulation by L-type channels. In both cases, systolic alternans follow, consistent with our experimental observations, being generated by propagating waves of Ca(2+) release and sustained through alternation of SR Ca(2+) content. This study provides novel and fundamental insights to understand mechanisms that may underlie intracellular Ca(2+) alternans without the need for refractoriness of L-type Ca or RyR channels under rapid pacing.
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