Fig. 1

Potential effects of inflammation,  exosomes, and microRNA (miRNA) on Ca²⁺ transport, storage and mitochondrial Ca²⁺ handling. Excitation–contraction (EC) coupling is initiated by an action potential which depolarizes the sarcolemma by rapid sodium (Na⁺) influx. Depolarization activates voltage-gated L-type Ca²⁺ channels (LTCC), and Ca²⁺ influx triggering calcium-induced calcium release (CICR) from the sarcoplasmic reticulum (SR) via the ryanodine receptor (RyR2). Rapid release of Ca²⁺ from the SR increases free intracellular Ca²⁺, enabling muscle contraction. Cardiomyocyte relaxation is regulated by signaling pathways that restore intracellular and SR Ca²⁺ to resting concentrations. Ca²⁺-activated kinases phosphorylate phospholamban (PLB), relieving its repression on Sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA2a). Consequently, SERCA2a rapidly imports Ca²⁺ into the SR, decreasing the intracellular Ca²⁺ concentration. Na⁺/Ca²⁺ exchangers (NCX) are allosterically activated by Ca²⁺ and aid in restoring resting Ca²⁺ concentrations; decreased cytosolic Ca²⁺ leads to relaxation of the sarcomere. Genes downregulated in DCM are denoted by a blue downward arrow and genes upregulated during DCM are denoted by a red upward arrow. Mitochondria is an energy mobilization and  Ca²⁺-buffering organelle. The Ca²⁺ homeostasis is controlled by its uptake through the mitochondrial Ca²⁺ uniporter (MCU) complex and voltage-dependent channel proteins, Ca²⁺ efflux is controlled by NCX. Exosomes and miRNAs control the gene expression of certain inflammatory cytokines, Ca²⁺ handling and signaling proteins. DHPR Dihydropyridine receptor; BIN1 bridging integrator 1; PMCA Sarcolemmal/plasma membrane Ca²⁺-ATPase; CSQ calsequestrin, mNCX Mitochondrial N⁺/Ca²⁺ exchanger; TNF-α Tumor necrosis factor-α; IL1b Interleukin 1β