Model parameters.

aOff-rates for ISO ≥4/min [9], epinephrine >100/min [10]. For a Kd of 450 nM (epinephrine) and 283 nM (ISO) the calculated on-rates are very fast. Slowing down the forward-rates to 500/min does not affect the downstream events being simulated since they happen at a slower time scale. The ligand off-rate is not set at lower than 4/min in order to avoid making it rate limiting for arrestin dissociation.
bα = Coupling efficiency relative to epinephrine; ISO is assumed to have the same coupling efficiency as epinephrine since they are both full agonists. The relative coupling efficiencies for partial agonists are as follows, Epinephrine = ISO = 1, Fenoterol = 0.66, Formoterol = 0.63, Terbutaline = 0.33, Zinterol = 0.33, Albuterol = 0.25, Salmeterol = 0.13, Dobutamine = 0.04 and Ephedrine = 0.03. [R*] = ([Rtotal] [Agonist]/([Agonist]+(Kd agonist)); [Rtotal] = 1; Kd epinephrine = 450 nM; Kd ISO = 283 nM. Simulated phosphorylation rate = α[R*]1.4 (for epinephrine); = α[R*]0.7 (for ISO).