ArticleCardiovascular research2022
Electrophysiological heterogeneity in large populations of rabbit ventricular cardiomyocytes.
Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Multiscale Electrophysiological Remodeling in Ischemic Heart Failure: Simulation Analysis of Ventricular Ectopic Activation.Biomedicines · 2026Article
- Role of natural inter-individual variability in the different penetrance of congenital long QT syndromes (LQTS) types 1 and 2: an in silico approach.Scientific reports · 2026Article
- Toward Standardized Methodologies for Drug-Induced Proarrhythmia Classification: An In Silico Proof of Concept.Computational and structural biotechnology journal · 2026Article
- GSNOR deletion differentially alters age-related cardiac function in a sex-dependent manner.American journal of physiology. Heart and circulatory physiology · 2026Article
- Beneficial action potential duration-shortening effects, but deleterious negative inotropism of IKs-activator docosahexaenoyl glycine in long QT syndrome type 2.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- Reduced gap junction coupling amplifies the effects of cardiomyocyte variability and destabilizes the heartbeat.Physiological reports · 2025Article
- Computational modelling for improved translation of cardiac inotropic and lusitropic drug effects from rats to humans.Journal of pharmacological and toxicological methods · 2025Article
- A large population of cell-specific action potential models replicating fluorescence recordings of voltage in rabbit ventricular myocytes.Royal Society open science · 2025Article
- Article
- Electrophysiological tolerance: a new concept for understanding the electrical stability of the heart.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Review
- Stem cell-derived cardiomyocyte heterogeneity confounds electrophysiological insights.The Journal of physiology · 2024Review
- Reduced connexin-43 expression, slow conduction and repolarisation dispersion in a model of hypertrophic cardiomyopathy.Disease models & mechanisms · 2024Article
- Cell-to-cell heterogeneity in ion channel conductance impacts substrate vulnerability to arrhythmia.American journal of physiology. Heart and circulatory physiology · 2024Article
- Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation.Physiological reviews · 2024Review
- Relationship between ion currents and membrane capacitance in canine ventricular myocytes.Scientific reports · 2024Article
- High-throughput methods for cardiac cellular electrophysiology studies: the road to personalized medicine.American journal of physiology. Heart and circulatory physiology · 2024Review
- In situ monolayer patch clamp of acutely stimulated human iPSC-derived cardiomyocytes promotes consistent electrophysiological responses to SK channel inhibition.Scientific reports · 2024Article
- Contractility measurements for cardiotoxicity screening with ventricular myocardial slices of pigs.Cardiovascular research · 2023Article
- Estimating the probability of early afterdepolarizations and predicting arrhythmic risk associated with long QT syndrome type 1 mutations.Biophysical journal · 2023Article
- Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsCardiac electrophysiological heterogeneity includes: (i) regional differences in action potential (AP) waveform, (ii) AP waveform differences in cells isolated from a single region, (iii) variability of the contribution of individual ion currents in cells with similar AP durations (APDs). The aim of this study is to assess intra-regional AP waveform differences, to quantify the contribution of specific ion channels to the APD via drug responses and to generate a population of mathematical models to investigate the mechanisms underlying heterogeneity in rabbit ventricular cells. METHODS AND
resultsAPD in ∼50 isolated cells from subregions of the LV free wall of rabbit hearts were measured using a voltage-sensitive dye. When stimulated at 2 Hz, average APD90 value in cells from the basal epicardial region was 254 ± 25 ms (mean ± standard deviation) in 17 hearts with a mean interquartile range (IQR) of 53 ± 17 ms. Endo-epicardial and apical-basal APD90 differences accounted for ∼10% of the IQR value. Highly variable changes in APD occurred after IK(r) or ICa(L) block that included a sub-population of cells (HR) with an exaggerated (hyper) response to IK(r) inhibition. A set of 4471 AP models matching the experimental APD90 distribution was generated from a larger population of models created by random variation of the maximum conductances (Gmax) of 8 key ion channels/exchangers/pumps. This set reproduced the pattern of cell-specific responses to ICa(L) and IK(r) block, including the HR sub-population. The models exhibited a wide range of Gmax values with constrained relationships linking ICa(L) with IK(r), ICl, INCX, and INaK.
conclusionModelling the measured range of inter-cell APDs required a larger range of key Gmax values indicating that ventricular tissue has considerable inter-cell variation in channel/pump/exchanger activity. AP morphology is retained by relationships linking specific ionic conductances. These interrelationships are necessary for stable repolarization despite large inter-cell variation of individual conductances and this explains the variable sensitivity to ion channel block.
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