Figure 5

Dynamic roles for feedback and feed-forward loops in the β-adrenergic network. Time courses of PLB activation in response to transient NE exposures (NE = 1) with several network perturbations. The thick solid line is the response of the default model, showing moderate PLB activation and damped oscillations. Also shown are simulations in which either the inhibitor-1 coherent positive feed-forward loop (thick dashed line; W_PKAC-Inhib1 = 0), the GRK negative feedback loop (thin dashed line; W_GRK-B1ARPG = 0) or the PKAC negative feedback loop (thin solid line; W_PKAC-B1ARPA = 0) were eliminated. Inhibitor-1 amplified PLB activation without affecting PLB dynamics. Both GRK and PKAC feedback loops decreased PLB phosphorylation via β₁-adrenergic receptor desensitization, though PKAC controlled steady-state adaptation while GRK feedback dampened the PLB response.