![]() In the mammalian heart, AP shape and duration vary depending on the regions and chambers (atrial vs. Na V1.5 plays a vital role in the generation and propagation of electrical impulses throughout the heart 1, and its activation contributes to the rising phase (phase 0) of cardiac action potentials (APs). The voltage-gated sodium channel (VGSC) α subunit, Na V1.5, which is encoded by the SCN5A gene, is the predominant Na + channel in the heart. Our results show that a RA treatment made it possible to obtain atrial cardiomyocytes and investigate differences in Na V1.5 channel properties between ventricular- and atrial-like cells. These differences could be explained by an increase in SCN2B regulatory subunit expression and a decrease in SCN1B and SCN4B regulatory subunit expressions. Moreover, Na + currents exhibited differences in activation and inactivation parameters. Interestingly, Na V1.5 channels in atrial cardiomyocytes exhibited lower mRNA transcripts and protein expression, which could explain the lower current densities recorded by patch-clamp. The amplitude, duration, and steady-state phase of APs in atrial cardiomyocytes decreased, and had a shape similar to that of mature atrial cardiomyocytes. We evaluated mRNA transcript and protein expressions to show that atrial cardiomyocytes expressed higher atrial- and sinoatrial-specific markers ( MYL7, CACNA1D) and lower ventricular-specific markers ( MYL2, CACNA1C, GJA1) than ventricular cardiomyocytes. The electrophysiological properties of action potentials (APs), Ca 2+ dynamics, K + and Na + currents were investigated using patch-clamp and optical mapping approaches. The quality of the atrial specification was assessed by qPCR, immunocytofluorescence, and western blotting. Atrial cardiomyocytes were obtained by the differentiation of hiPSCs treated with retinoic acid (RA). The objective of the present study was to investigate the molecular, electrical, and biophysical properties of several ion channels, especially Na V1.5 channels, in atrial hiPSC cardiomyocytes. However, it is essential to obtain a comprehensive understanding of the electrophysiological properties of these cells. Generating atrial-like cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) is crucial for modeling and treating atrial-related diseases, such as atrial arrythmias including atrial fibrillations.
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