Calcium handling properties in human embryonic stem cell-derived cardiomyocytes. (A,B) Schematic showing calcium signaling pathways in adult cardiomyocytes (CM) (A) and human pluripotent stem cell-derived CMs (hPSC-CMs). hPSC-CMs show a smaller calcium transient amplitude, slower kinetics and absence of inotropic responses compared to adult CMs due to 1) lack of junctin and triadin to facilitate ryanodine receptor (RyR) function; 2) lack of calsequestrin for sarcoplasmic reticulum (SR) calcium buffering; 3) lack of phospholamban for sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) modulation; 4) lower SERCA and RyR expression; 5) lack of T-tubules leading to U-shape of calcium propagation wavefront. (Adapted from Li et al. ). (C) Summary of differences in calcium transient properties between adult CMs and human embryonic stem cell-derived CMs (hESC-CMs). (Adapted from Kong et al. ).