Figure 1. Role of the MUC in Ca²⁺ homeostasis and energy production in cardiomyocytes. This figure illustrates that Ca²⁺ influx through L-type VDCCs stimulates the release of Ca²⁺ from the SR through the RyR, increasing the [Ca²⁺]_c. Ca²⁺ binds to TnC and promotes the interaction of TnC with TnI, causing TnI to move from the active site of the actin, allowing the displacement of TmT and TnT and muscle contraction (systole). This increase in [Ca²⁺]_c increases the Ca²⁺ influx into mitochondria via the MCU, stimulating ATP synthesis due to Ca²⁺-dependent activation of TCA cycle dehydrogenases. The increase in [Ca²⁺]_c is restored to basal levels (resting) by Ca²⁺ sequestration in the SR via SERCA and Ca²⁺ extrusion via PMCA and NCX, and this reduction in [Ca²⁺]_c promotes the relaxation of cardiac cells (diastole). Ionic and energetic collapse deregulates CECC, leading to heart failure. This collapse could be attenuated or prevented by selective MUC blockers, such as ruthenium red (RR) and their analogs. Adapted from Bers (28).