Exploring SCN5A variants associated with atrial fibrillation in atrial cardiomyocytes derived from human induced pluripotent stem cells: A characterization study.

Background: Atrial fibrillation (AF) poses a major risk for heart failure, myocardial infarction, and stroke. Several studies have linked SCN5A variants to AF, but their precise mechanistic contribution remains unclear. Human induced pluripotent stem cells (hiPSCs) provide a promising platform for modeling AF-linked SCN5A variants and their functional alterations.

Impacts of DCM-linked gating pore currents on the electrophysiological characteristics of hiPSC-CM monolayers.

Background: Variants of the SCN5A gene, which encodes the Na1.5 cardiac sodium channel, have been linked to arrhythmic disorders associated with dilated cardiomyopathy (DCM). However, the precise pathological mechanisms remain elusive.

Generation of a patient-specific iPSC cell line with cardiac arrhythmias and dilated cardiomyopathy (CBRCULi016-A), an isogenic control (CBRCULi016-A-1), and a paternal control (CBRCULi017-A).

Dilated cardiomyopathy (DCM) is a prevalent cause of heart failure. We generated induced pluripotent stem cell (iPSC) lines from a DCM patient carrying a mutation in the SCN5A gene, with his healthy father serving as a control. Notably, we employed CRISPR-Cas9 to rectify the mutation in the patient's iPSC line.

Biophysical properties of Na1.5 channels from atrial-like and ventricular-like cardiomyocytes derived from human induced pluripotent stem cells.

Generating atrial-like cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) is crucial for modeling and treating atrial-related diseases, such as atrial arrythmias including atrial fibrillations. However, it is essential to obtain a comprehensive understanding of the electrophysiological properties of these cells. The objective of the present study was to investigate the molecular, electrical, and biophysical properties of several ion channels, especially Na1.

Cardiac involvement in patient-specific induced pluripotent stem cells of myotonic dystrophy type 1: unveiling the impact of voltage-gated sodium channels.

Myotonic dystrophy type 1 (DM1) is a genetic disorder that causes muscle weakness and myotonia. In DM1 patients, cardiac electrical manifestations include conduction defects and atrial fibrillation. DM1 results in the expansion of a CTG transcribed into CUG-containing transcripts that accumulate in the nucleus as RNA foci and alter the activity of several splicing regulators.

Optical Mapping of Cardiomyocytes in Monolayer Derived from Induced Pluripotent Stem Cells.

Optical mapping is a powerful imaging technique widely adopted to measure membrane potential changes and intracellular Ca variations in excitable tissues using voltage-sensitive dyes and Ca indicators, respectively. This powerful tool has rapidly become indispensable in the field of cardiac electrophysiology for studying depolarization wave propagation, estimating the conduction velocity of electrical impulses, and measuring Ca dynamics in cardiac cells and tissues. In addition, mapping these electrophysiological parameters is important for understanding cardiac arrhythmia mechanisms.

Na1.5 knockout in iPSCs: a novel approach to study Na1.5 variants in a human cardiomyocyte environment.

Cardiomyocytes derived from patient-specific induced pluripotent stem cells (iPSC-CMs) successfully reproduce the mechanisms of several channelopathies. However, this approach involve cell reprogramming from somatic tissue biopsies or genomic editing in healthy iPSCs for every mutation found and to be investigated. We aim to knockout (KO) Na1.

iPSC-derived cardiomyocytes from patients with myotonic dystrophy type 1 have abnormal ion channel functions and slower conduction velocities.

Cardiac complications such as electrical abnormalities including conduction delays and arrhythmias are the main cause of death in individuals with Myotonic Dystrophy type 1 (DM1). We developed a disease model using iPSC-derived cardiomyocytes (iPSC-CMs) from a healthy individual and two DM1 patients with different CTG repeats lengths and clinical history (DM1-1300 and DM1-300). We confirmed the presence of toxic RNA foci and mis-spliced MBNL1/2 transcripts in DM1 iPSC-CMs.