Quantitative Modeling of GRK-Mediated β2AR Regulation
Figure 6
Simulations of the effects of frequency modulation.
In these panels we describe the effect of varying the frequency of stimulation on surface (black), phosphorylated (red) and active (green) receptor species. (A) Rapid stimulation with a train of 1 µM ISO pulses for 0.5 min followed by a 0.5 min immediate washout. Note that this achieves more than 80% desensitization with only 20% internalization. (B) This panels shows the results of a 5 min stimulation with 1.0 µM ISO and a 5 min washout. (C) Simulation of a prolonged 30 min stimulation with 50 nM ISO followed by washout of 30 min. This panel shows that even with low β2AR occupancy (15%) the prolonged stimulation time gives substantial desensitization.