Fig 6. Remodeling of Ca²⁺ handling proteins during atrial fibrillation and heart failure.

Changes in protein expression are indicated by arrows (orange color). Solid black arrows indicate transport directions of Ca²⁺ or Na⁺ ions, respectively. Decreased levels of Ca²⁺-calmodulin-dependent protein kinase (CaMK) IIδ and protein kinase A (PKA) causes hypophosphorylation of phospholamban (PLN) and ryanodine receptor (RyR) 2, leading to reduced Ca²⁺ uptake into the sarcoplasmic reticulum through sarcoplasmic reticulum Ca²⁺-ATPase (Serca) 2a. Increased intracellular Ca²⁺ levels and upregulation of Na⁺-Ca²⁺ exchanger (NCX) 1 expression enhance electrogenic Na⁺-Ca²⁺ exchange. This mechanism is attenuated by reduced L-type calcium channel (LTCC) expression that limits systolic Ca²⁺ influx.