Figure 8 .

The signaling pathways linking MO to fetal heart contractile dysfunction. MO activates phosphorylation of PKA and CaMKII which further activate SR Ca²⁺ release channel RyR2 at Ser²⁸⁰⁸ and Ser²⁸¹⁴, resulting in intracellular Ca²⁺ overload. On the other hand, MO decreases MHC-α and increases MHC-β. Meanwhile, MO increases cTn-T, phosphorylation of cTn-I, and tropomyosin, which lead to Ca²⁺ insensitivity of the myofilament. We conclude that intracellular Ca²⁺ overload and insensitivity are major causes of fetal cardiomyocyte contractile dysfunction and intracellular Ca²⁺ mishandling. Up arrows: up-regulation; down arrows: down-regulation.