Related Experiment Video

Updated: Nov 19, 2025

Isolation and Functional Characterization of Human Ventricular Cardiomyocytes from Fresh Surgical Samples
14:39

Isolation and Functional Characterization of Human Ventricular Cardiomyocytes from Fresh Surgical Samples

Published on: April 21, 2014

17.7K

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

Hugo Poulin1, Aurélie Mercier1, Mohammed Djemai1

  • 1CERVO Brain Research Centre, Quebec, QC, Canada.

Scientific Reports
|January 29, 2021
PubMed

Insights

Myotonic Dystrophy type 1 (DM1) cardiac dysfunction involves abnormal sodium and calcium channels in heart cells. This study models DM1 using patient-derived cells, revealing ion channel defects impacting heart electrical activity and conduction.

Area of Science:

  • Cardiovascular Biology
  • Genetics
  • Stem Cell Biology

Background:

  • Cardiac complications, including arrhythmias, are a primary cause of mortality in Myotonic Dystrophy type 1 (DM1).
  • DM1 is characterized by CTG repeat expansions, leading to toxic RNA foci and MBNL1/2 mis-splicing, impacting cellular function.

Purpose of the Study:

  • To develop and characterize an induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model of DM1.
  • To investigate the ion channel dysfunctions underlying cardiac electrical abnormalities in DM1 patients.

Main Methods:

  • Generation of iPSC-CMs from healthy individuals and DM1 patients with varying CTG repeat lengths.
  • Confirmation of toxic RNA foci and MBNL1/2 mis-splicing in DM1 iPSC-CMs.
  • Electrophysiological assessments (e.g., optical mapping, ion current measurements) and molecular analyses (e.g., transcript/protein expression).

Main Results:

  • DM1 iPSC-CMs exhibited toxic RNA foci and MBNL1/2 mis-splicing.
  • A switch from adult to neonatal SCN5A isoforms and increased L-type calcium current (ICaL) density were observed in DM1-1300 iPSC-CMs.
  • Ion channel dysfunctions (INa and ICaL) led to prolonged action potential duration, slower conduction velocities, and decreased action potential upstrokes.

Conclusions:

  • DM1 iPSC-CMs recapitulate key cardiac electrical abnormalities seen in patients.
  • Distinct perturbations in sodium (Na+) and calcium (Ca2+) channels contribute to cardiac dysfunction in DM1.
  • These ion channel defects significantly impact cardiac action potentials and overall heart conduction.

More Related Videos

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers14:03

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers

Published on: March 24, 2023

2.2K
Sarcomere Shortening of Pluripotent Stem Cell-Derived Cardiomyocytes using Fluorescent-Tagged Sarcomere Proteins.08:37

Sarcomere Shortening of Pluripotent Stem Cell-Derived Cardiomyocytes using Fluorescent-Tagged Sarcomere Proteins.

Published on: March 3, 2021

4.7K

Related Concept Videos

EPS and iPS Cells in Disease Research01:21

EPS and iPS Cells in Disease Research

Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
3.1K
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
148
iPS Cell Differentiation01:22

iPS Cell Differentiation

The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
2.9K