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Hipsc-derived Cardiomyocytes As A Model To Study The Role Of Small-conductance Ca2+-activated K+ (sk) Ion Channel Variants Associated With Atrial Fibrillation.

Home
Research Domains
Biomedical And Clinical Sciences
Oncology And Carcinogenesis
Predictive And Prognostic Markers
Hipsc-derived Cardiomyocytes As A Model To Study The Role Of Small-conductance Ca2+-activated K+ (sk) Ion Channel Variants Associated With Atrial Fibrillation.

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Published on: July 3, 2013

hiPSC-derived cardiomyocytes as a model to study the role of small-conductance Ca²⁺-activated K⁺ (SK) ion channel variants associated with atrial fibrillation.

Hosna Babini^1,2, Verónica Jiménez-Sábado^1,2,3, Ekaterina Stogova^1,2

¹Cellular and Regenerative Medicine Centre, BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Frontiers in Cell and Developmental Biology

|February 2, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Keywords:

atrial fibrillation calcium cardiac action potential cardiomyocytes

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Isolation of Atrial Myocytes from Adult Mice

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Published on: July 25, 2019

Researchers are investigating a specific genetic variant (rs13376333) linked to atrial fibrillation (AF). This study aims to determine if the variant affects the KCNN3 gene

Area of Science:

Cardiovascular Genetics
Electrophysiology
Stem Cell Biology

Background:

Atrial fibrillation (AF) is the most common arrhythmia, linked to genetic and molecular changes in atrial cells.
Genome-wide association studies (GWAS) identified the rs13376333 single nucleotide polymorphism (SNP) in the 1q21 region as significantly associated with AF.
This SNP is intronic to the KCNN3 gene, which encodes small conductance calcium-activated potassium channels type 3 (SK3), crucial for atrial excitability.

Purpose of the Study:

To elucidate the functional electrophysiological effects of the rs13376333 risk SNP.
To determine if the rs13376333 SNP represents a gain-of-function (GoF) or loss-of-function (LoF) variant.
To highlight the utility of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for studying AF-associated genetic variants.

human induced pluripotent stem cells

single nucleotide polymorphisms

small-conductance Ca2+-activated K+ channels

Main Methods:

Review of existing literature on SK channel function, AF pathophysiology, and KCNN3 risk SNPs.
Discussion of the potential of human induced pluripotent stem cells (hiPSCs) and derived cardiomyocytes (hiPSC-CMs) as a model system.
Exploration of genetic editing tools and 3D bioprinting for creating advanced atrial tissue models.

Main Results:

The precise electrophysiological impact of the rs13376333 SNP on SK3 channels and AF development remains unknown.
Both increased and decreased SK3 channel activity can contribute to arrhythmias via distinct mechanisms.
hiPSC-CMs offer a promising human-centric model to overcome limitations of animal and native cell studies.

Conclusions:

Understanding the functional consequences of AF-associated SNPs like rs13376333 is vital for personalized medicine and risk stratification.
hiPSC-CMs, combined with genetic engineering and 3D bioprinting, represent a powerful platform for investigating AF mechanisms.
Further research with hiPSC-derived models is essential for advancing our knowledge of AF genetics and developing targeted therapies.