Figure 8.

Overall schematic for PLM's role in β-adrenergic signaling. 1, SR Ca²⁺ load specifies the size of Ca²⁺ transients during CICR. 2, PLB increases SR load by biasing diastolic Ca²⁺ extrusion toward SERCA. 3, PLM decreases SR load by driving Na⁺ extrusion and biasing diastolic Ca²⁺ extrusion toward NCX. 4, Ca²⁺ adaptation occurs because Na⁺/K⁺ dynamics lag behind SERCA dynamics. 5, Receptor desensitization weakly contributes to Ca²⁺ adaptation, highlighting a negative feed-forward loop formed by PLB and PLM. This negative feed-forward network motif accelerates β-adrenergic inotropy.