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

In clinical settings, patients with SNTA1 point mutations are often associated with rare arrhythmias, including Long QT syndrome, Brugada syndrome, and sudden infant death syndrome. Previous studies on SNTA1 have predominantly utilized nonhuman cardiomyocyte models. This study aims to elucidate the phenotype of SNTA1 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 action potential duration (FPD) and slower conduction velocity, as detected by micro electrode array analysis. Immunofluorescence analysis further revealed disorganized distribution of SCN5A protein 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 SCN5A in human cardiomyocytes.