Cardiac electrophysiology and arrhythmias

Computational Study of the Excitation of Human Induced Pluripotent Stem-Cell Derived Cardiomyocytes

This study modifies a computational model of hiPSC-CMs to compare their excitation properties with hV-CMs under various conditions and finds hiPSC-CMs are more excitable due to their depolarized resting potential and intrinsic automaticity.

Sudden Death-Associated KCNH2 Variants Have Opposing Effects on hERG1NP Function

This study examines hERG1NP variants linked to sudden death, finding some reduce and others increase hERG1NP activity through different mechanisms.

Calcium transient was triggered by Na+ influx in phase 0 and regulated by Ca2+ influx in phase 2 of the action potential in adult rat left ventricular cardiomyocyte

The paper investigates the role of Na+ and Ca2+ influx in triggering and regulating the calcium transient during the action potential in adult rat cardiomyocytes.

High Throughput Screening Identifies a Small Molecule Trafficking Corrector for Long-QT Syndrome Associated KCNQ1 Variants

This study identifies a small molecule, VU0494372, that enhances KCNQ1 expression and trafficking, offering a potential therapeutic approach for LQTS.

Adrenergic Hypersensitivity Drives Ventricular Arrhythmias Following Loss of Plexin-Mediated Cardiac Innervation

This study shows that loss of plexin-mediated cardiac innervation leads to adrenergic hypersensitivity and ventricular arrhythmias in mice, with human PLXNA4 variants linked to arrhythmias.

Mechanistic Insights into Sex Differences in Atrial Electrophysiology and Arrhythmia Vulnerability through Sex-specific Computational Models.

This paper develops and validates sex-specific computational models of human atrial cardiomyocytes to investigate sex differences in atrial fibrillation mechanisms and therapeutic responses.

Human Engineered Heart Tissue Models for Pharmacological Studies- Inhibition of Small-Conductance Ca2+-activated K+ (KCa2) channel

The paper develops chamber-specific 3D human Engineered Heart Tissue (EHT) models to study KCa2 channel inhibitors and their effects on atrial fibrillation.

Prediction of TdP Arrhythmia Risk Through Molecular Simulations of Conformation-specific Drug Interactions with the hERG K+, NaV1.5, and CaV1.2 Channels

Computational Modeling and Visualization of Ischemic Effects on an Advanced Purkinje Network

This study presents a computational model of the Purkinje network that simulates ischemic effects on conduction and refractoriness, providing insights into arrhythmogenic risk.

Late INa activation of cardiac TTX-sensitive sodium channels by AaH-II induces an arrhythmogenic phenotype

This study shows that AaH-II selectively activates TTX-S Nav channels, inducing arrhythmias in cardiac tissue, and suggests targeting these channels as an antiarrhythmic strategy.

CaMKII Phosphorylation of RyR2 is Essential for Arrhythmia in CPVT

This study shows that CaMKII phosphorylation of RYR2 at S2814 is essential for arrhythmia in CPVT, acting as an intra-molecular event.

Arrhythpy: An Automated Tool to Quantify and Classify Arrhythmias in Ca2+ Transients of iPSC-Cardiomyocytes

Arrhythpy quantifies and classifies arrhythmias in iPSC-CMs using Ca2+ transients, showing its utility in disease models and drug response analysis.

A role of extracellular vesicle-mediated inter-organ communication in obesity-related arrhythmia

This paper shows that obesity-related extracellular vesicles from visceral adipose tissue impair cardiac function and contribute to arrhythmia by affecting cardiomyocytes, fibroblasts, and macrophages.

Repurposing polyamines to prevent arrhythmias in Short QT Syndrome type 3, a potentially lethal disease

This study shows that polyamine administration can prolong cardiac repolarization and reduce arrhythmias in a mouse model of SQTS3 caused by Kir2.1M301K mutation.

Transgenic mice overexpressing Pitx2 in the atria develop tachycardia-bradycardia syndrome

This study shows that overexpression of Pitx2c in the atria of mice leads to SAN dysfunction and TBS-like pathology, including prolonged SAN recovery time and increased AF inducibility.

Large-scale synthetic data enable digital twins of human excitable cells

The paper uses synthetic data to create digital twins of human cardiomyocytes, enabling precise modeling of electrophysiological properties from experimental recordings.

Non-canonical Sodium Channel Isoforms Underlie Chamber Specific Cardiac Excitability

This study identifies chamber-specific contributions of non-NaV1.5 sodium channel isoforms to cardiac excitability using a chemical-genetic mouse model and electrophysiological recordings.

Cardiac-specific Kv1.1 deficiency alters cardiomyocyte electrophysiology without modifying overall cardiac function or arrhythmia susceptibility

This study shows that cardiac-specific Kv1.1 deficiency impairs atrial repolarization but does not cause overall cardiac dysfunction or arrhythmia susceptibility.

Dysferlin Regulates Cardiac T-tubule Structure and Excitation-contraction Coupling in Isolated Cardiac Myocytes at Rest and in Response to Acute Hypo-osmotic Stress and is Protective Against Arrhythmias in Langendorff-perfused Hearts

This study shows dysferlin is critical for maintaining cardiac T-tubule structure and EC coupling, and its loss increases arrhythmia risk under stress and during aging.

The sodium/glucose cotransporter 2 inhibitor empagliflozin is a pharmacological chaperone of cardiac Nav1.5 channels

This study shows empagliflozin enhances peak sodium current in Nav1.5 channels by acting as a pharmacological chaperone, potentially reducing arrhythmia risk in Duchenne muscular dystrophy.

Ablation of three major phospho-sites in RyR2 preserves the global adrenergic response but creates an arrhythmogenic substrate

This study shows that ablating three key phospho-sites in RyR2 preserves adrenergic responses but increases arrhythmogenic risk by altering Ca2+ leak and promoting early afterdepolarizations.

The NaV1.5 auxiliary subunit FGF13 modulates channels by regulating membrane cholesterol independent of channel binding

This study shows FGF13 modulates VGSCs by regulating membrane cholesterol, independent of direct channel binding, and reveals its role in maintaining cholesterol distribution and VGSC localization at the intercalated disc.

Sex-specific human electromechanical multiscale in-silico models for virtual therapy evaluation

This paper develops sex-specific human electromechanical models to simulate and evaluate sex differences in drug responses and ECG biomarkers, revealing ionic and anatomical mechanisms underlying these differences.

DECREASING TRANSMURAL DISPERSION OF VENTRICULAR ACTION POTENTIAL REPOLARIZATION WITH MULTICHANNEL PHARMACOLOGY

The paper identifies two strategies using multichannel pharmacology to prolong action potential duration while reducing transmural dispersion of repolarization in cardiac myocytes.

Dilated cardiomyopathy remodels cardiac neuronal subtypes in a murine model

The paper identifies a cardiac neuronal subtype, NA1b, that increases in a murine dilated cardiomyopathy model and shows elevated M-current ion channels and neurodegenerative pathways.

Patient-derived Cellular Models of Polygenic Scores: Application to Long QT Syndrome

The paper uses patient-derived iPSC-CMs to show that polygenic scores influence cardiac electrophysiology and drug response in Long QT Syndrome.

SYNPO2L Isoforms Regulate the Action Potential Characteristics and Contractility of Atrial Cardiomyocytes via YAP Signaling to Modulate Atrial Fibrillation Risk

This study shows that a rare splice mutation in SYNPO2L leads to increased SYNPO2L_B isoform expression, impairing atrial cardiomyocyte function, and that restoring SYNPO2L_A improves electrophysiology and contractility via YAP signaling.

AAV6-HCN4t-mediated biological pacing as a potential life-saving therapy for congenital complete heart block

This study develops AAV6-HCN4t gene therapy to enhance biological pacing in complete heart block, showing sustained effects in rats and pigs.

Genomic and molecular evidence that the lncRNA DSP-AS1 modulates Desmoplakin expression

The paper identifies a variant in DSP associated with QRS interval and shows that DSP-AS1 regulates DSP expression through functional and Mendelian randomization analyses.

Coordinated Tbx3/Tbx5 transcriptional control of the adult ventricular conduction system

This study shows that Tbx3 and Tbx5 work together to control the function and molecular identity of the adult ventricular conduction system in mice, leading to conduction defects when both are missing.