Academic Journal
hiPSC-derived cardiomyocytes as a model to study the role of small-conductance Ca2+-activated K+ (SK) ion channel variants associated with atrial fibrillation
| العنوان: | 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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| المؤلفون: | Babini, Hosna, Jiménez-Sábado, Verónica, Stogova, Ekaterina, Arslanova, Alia, Butt, Mariam, Dababneh, Saif, Asghari, Parisa, Moore, Edwin DW, Claydon, Thomas W, Chiamvimonvat, Nipavan, Hove-Madsen, Leif, Tibbits, Glen F |
| بيانات النشر: | eScholarship, University of California |
| سنة النشر: | 2024 |
| المجموعة: | University of California: eScholarship |
| مصطلحات موضوعية: | Biological Sciences, Medical Physiology, Biomedical and Clinical Sciences, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Cardiovascular, Stem Cell Research, Heart Disease, 2.1 Biological and endogenous factors, Good Health and Well Being, small-conductance Ca2+-activated K+ channels, atrial fibrillation, calcium, cardiac action potential, single nucleotide polymorphisms, human induced pluripotent stem cells, cardiomyocytes |
| الوصف: | Atrial fibrillation (AF), the most common arrhythmia, has been associated with different electrophysiological, molecular, and structural alterations in atrial cardiomyocytes. Therefore, more studies are required to elucidate the genetic and molecular basis of AF. Various genome-wide association studies (GWAS) have strongly associated different single nucleotide polymorphisms (SNPs) with AF. One of these GWAS identified the rs13376333 risk SNP as the most significant one from the 1q21 chromosomal region. The rs13376333 risk SNP is intronic to the KCNN3 gene that encodes for small conductance calcium-activated potassium channels type 3 (SK3). However, the functional electrophysiological effects of this variant are not known. SK channels represent a unique family of K+ channels, primarily regulated by cytosolic Ca2+ concentration, and different studies support their critical role in the regulation of atrial excitability and consequently in the development of arrhythmias like AF. Since different studies have shown that both upregulation and downregulation of SK3 channels can lead to arrhythmias by different mechanisms, an important goal is to elucidate whether the rs13376333 risk SNP is a gain-of-function (GoF) or a loss-of-function (LoF) variant. A better understanding of the functional consequences associated with these SNPs could influence clinical practice guidelines by improving genotype-based risk stratification and personalized treatment. Although research using native human atrial cardiomyocytes and animal models has provided useful insights, each model has its limitations. Therefore, there is a critical need to develop a human-derived model that represents human physiology more accurately than existing animal models. In this context, research with human induced pluripotent stem cells (hiPSC) and subsequent generation of cardiomyocytes derived from hiPSC (hiPSC-CMs) has revealed the underlying causes of various cardiovascular diseases and identified treatment opportunities that were not possible using in ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| Relation: | qt7x76n2rp; https://escholarship.org/uc/item/7x76n2rp; https://escholarship.org/content/qt7x76n2rp/qt7x76n2rp.pdf |
| DOI: | 10.3389/fcell.2024.1298007 |
| الاتاحة: | https://escholarship.org/uc/item/7x76n2rp https://escholarship.org/content/qt7x76n2rp/qt7x76n2rp.pdf https://doi.org/10.3389/fcell.2024.1298007 |
| Rights: | CC-BY |
| رقم الانضمام: | edsbas.F47D037E |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fcell.2024.1298007 |
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