Cav1.3-C-terminus Restores Electrical and Contractile Functions in hiPSC-derived Cardiomyocytes Model of Heart Failure

AAV6-delivered Cav1.3-C-terminus restores chronotropic and inotropic function in ET-1–treated hiPSC-derived cardiomyocyte monolayers, returning action potential duration and current densities to control levels.

• Why it matters: Heart failure involves excitation–contraction coupling failure and structural remodeling, and ET-1–induced models capture these dysregulations; a transcriptional regulator that reverses both electrophysiology and contractility is needed.
• What they did: hiPSC-CM monolayers were exposed to 10 nM endothelin-1 for 48 hours, then co-treated with AAV6-Cav1.3-C-terminus; RT-qPCR, patch-clamp, and video-based contractility analysis were used.
• The result: ET-1 increased NPPA, NPPB, ACTA1, and COL1A1 and altered membrane capacitance, while downregulating KCNH2, CACNA1D, CACNA1C, and SCN5A, reducing K/Ca/Na currents and prolonging APD; Cav1.3-C-terminus normalized CACNA1D and KCNH2 expression, current densities, APD, and fully restored beating rate and contraction amplitude to control.