Figure 7.

Ca²⁺ adaptation is explained by a negative feed-forward loop. A, Steady-state SR load is better explained by PLM phosphorylation than β-AR desensitization. B, PLM phosphorylation contributes more strongly limits cytosolic Ca²⁺ transients than β-AR desensitization. C, WT Ca²⁺ adaptation is associated with slow intracellular Na⁺ dynamics. D, Accelerating intracellular Na⁺ dynamics block Ca²⁺ adaptation in WT myocytes, indicating a negative feed-forward regulatory motif. E, The model predicts accelerated inotropic responses to ISO in WT myocytes over PLM-KO myocytes. F, Reanalyzed experimental data validates this model prediction in cardiac myocytes [5] and G, also indicates this acceleration occurs in the intact heart [33].