Regulation of APD and Force by the Na+/Ca2+ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue
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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 < 0.05). SEA0400 (10 mu M) markedly shortened the APD(90) in EHT (by 26.6 +/- 5%, p < 0.05) and, to a lesser extent, in rat ventricular tissue (by 10.7 +/- 1.6%, p < 0.05). Shortening in human left ventricular preparations was small and not different from time-matched controls (TMCs; p > 0.05). Force was increased by the NCX block in rat ventricle (by 31 +/- 5.4%, p < 0.05) and EHT (by 20.8 +/- 3.9%, 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.
Original language | English |
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Article number | 2424 |
Journal | Cells |
Volume | 11 |
Issue number | 15 |
Number of pages | 15 |
ISSN | 2073-4409 |
DOIs | |
Publication status | Published - 2022 |
- hiPSC-CM, human ventricular cardiomyocytes, rat ventricular cardiomyocytes, NCX, APD, force, SEA0400, SODIUM-CALCIUM EXCHANGER, NA+-CA2+ EXCHANGER, SEA0400 FAILS, CA2+ CURRENT, INHIBITION, CANINE, CARDIOMYOCYTES, ARRHYTHMOGENESIS, CONTRACTILITY, ARRHYTHMIAS
Research areas
ID: 317740162