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<p>In clinical settings, patients with α-1-syntrophin point mutations are often associated with rare arrhythmias, including Long QT syndrome, Brugada syndrome, and sudden infant death syndrome. Previous studies on α-1-syntrophin have predominantly utilized nonhuman cardiomyocyte models. This study aims to elucidate the phenotype of α-1-syntrophin deficiency using human cardiomyocytes. Using CRISPR/Cas9 technology, we generated <i>SNTA1</i> knockout (KO) embryonic stem cell line, which were subsequently differentiated into cardiomyocytes using 2D differentiation method. Genotype analysis identified an adenine (A) insertion in the second exon of <i>SNTA1</i>, resulting in a premature stop codon at the 149th amino acid position and truncation within the PDZ domain. <i>SNTA1</i>-deficient cardiomyocytes exhibited a shortened field potential duration (FPD) and slower conduction velocity, as detected by micro electrode array analysis. Immunofluorescence analysis further revealed disorganized distribution of Nav1.5 in <i>SNTA1</i>-deficient cardiomyocytes. <i>SNTA1</i> is a susceptibility locus for arrhythmias and plays a critical role as an essential auxiliary protein in the proper localization of Nav1.5 in human cardiomyocytes.</p>

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SNTA1-deficient human cardiomyocytes show shorter field potential duration and slower conduction velocity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月20日

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  • Tao Dong,
  • Yan Zhao,
  • Meng Zhang,
  • Wei-Ya Lang,
  • Dan-Yang Liu,
  • Ke-Shuang Zhang,
  • Yue-Jing Wang,
  • Lin Li,
  • Jie Lian,
  • Hong-Bo Yao,
  • Hai-Yan Zhang,
  • Hai-Feng Jin,
  • Tong Lu,
  • Lei Shen,
  • Li-Ling Yue,
  • Yan Lin

摘要

In clinical settings, patients with α-1-syntrophin point mutations are often associated with rare arrhythmias, including Long QT syndrome, Brugada syndrome, and sudden infant death syndrome. Previous studies on α-1-syntrophin have predominantly utilized nonhuman cardiomyocyte models. This study aims to elucidate the phenotype of α-1-syntrophin deficiency using human cardiomyocytes. Using CRISPR/Cas9 technology, we generated SNTA1 knockout (KO) embryonic stem cell line, which were subsequently differentiated into cardiomyocytes using 2D differentiation method. Genotype analysis identified an adenine (A) insertion in the second exon of SNTA1, resulting in a premature stop codon at the 149th amino acid position and truncation within the PDZ domain. SNTA1-deficient cardiomyocytes exhibited a shortened field potential duration (FPD) and slower conduction velocity, as detected by micro electrode array analysis. Immunofluorescence analysis further revealed disorganized distribution of Nav1.5 in SNTA1-deficient cardiomyocytes. SNTA1 is a susceptibility locus for arrhythmias and plays a critical role as an essential auxiliary protein in the proper localization of Nav1.5 in human cardiomyocytes.