Figure 9

cAMP dynamics obtained with different initial amounts of Pde1 and Pde2. Dynamics of cAMP with different initial amounts of the phosphodiesterases, as given in Figure 8, where A: Pde1 = 0, Pde2 = 0; B: Pde1 = 0, Pde2 = 13,000; C: Pde1 = 2,800, Pde2 = 0; D: Pde1 = 2,800, Pde2 = 13,000 molecules. The plots show that in the absence of both phosphodiesterases (A) we achieve, as expected, an unlimited accumulation of cAMP, since our model does not include any other mechanism to reduce the intracellular level of cAMP; with a very high initial amount of Pde2 (B and D), cAMP reaches a noisy steady state but no oscillations are observed; in the absence of Pde2, when only Pde1 is active (C), oscillations of cAMP can then be established, showing a very large amplitude and a mean cAMP amount that is slightly higher than standard conditions. The molecular amounts of cAMP reached in conditions A and C are higher than the physiological levels measured in corresponding experimental settings [12, 14] though, from a computational point of view, they are indicative of the role played by the two phosphodiesterases, since they highlight the different dynamical behaviors of the pathway in extreme conditions.