FIGURE 1.

Differences in calcium regulation between adult human cardiomyocytes and in hiPSC-derived cardiomyocytes. In adult human cardiomyocytes (left), T-tubules result in close proximity between L-type Ca²⁺ channels and RyR2 allowing for a larger release of Ca²⁺ from the SR, quickly diffusing into the cytosol and going to the myofilaments to facilitate contraction as well as into closely tethered mitochondria to stimulate ATP production. Ca²⁺ is then primarily sequestered back into the SR via SERCA. In hiPSC-CMs (right), increased distance between L-type calcium channels and RyR2 results in less Ca²⁺ release from the SR, requiring the cells to rely more heavily on L-type Ca²⁺ influx to facilitate contraction. After relaxation a larger fraction of the cytosolic Ca²⁺ is removed via the Na⁺/Ca²⁺ exchanger.