Regulation of APD and Force by the Na⁺/Ca²⁺ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue

Abstract

The physiological importance of NCX in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is not well characterized but may depend on the relative strength of the current, compared to adult cardiomyocytes, and on the exact spatial arrangement of proteins involved in Ca2+ extrusion. Here, we determined NCX currents and its contribution to action potential and force in hiPSC-CMs cultured in engineered heart tissue (EHT). The results were compared with data from rat and human left ventricular tissue. The NCX currents in hiPSC-CMs were larger than in ventricular cardiomyocytes isolated from human left ventricles (1.3 ± 0.2 pA/pF and 3.2 ± 0.2 pA/pF for human ventricle and EHT, respectively, p 90 in EHT (by 26.6 ± 5%, p p p > 0.05). Force was increased by the NCX block in rat ventricle (by 31 ± 5.4%, p p < 0.05), but not in human left ventricular preparations. In conclusion, hiPSC-CMs possess NCX currents not smaller than human left ventricular tissue. Robust NCX block-induced APD shortening and inotropy makes EHT an attractive pharmacological model.

Keywords

• hiPSC-CM
• human ventricular cardiomyocytes
• rat ventricular cardiomyocytes
• NCX
• APD
• force