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A Kinetic Model of Dopamine- and Calcium-Dependent Striatal Synaptic Plasticity

Figure 13

Robustness of the PKA-PP2A-DARPP-32 positive feedback loop.

(A–C) Robustness of the threshold-like PKA activation as a function of total concentration of Cdk5 in the sub-system shown in Fig. 9, when three parameters were independently altered: (A) A dissociation constant Kd in a reaction where Thr75 is dissociated from inhibited PKA, was given by (blue), (cyan), (green), (orange), (magenta) or (red); (B) A catalytic constant in a reaction where active PKA phosphorylates PP2A, is given by 10 times (black), 5 times (blue), 2 times (green), control (yellow), 0.5 times (orange), 0.2 times (magenta), 0.1 times (red), larger than the control value in the original model (yellow); and (C) A catalytic constant in a reaction where active PP2A dephosphorylates Thr75, is given by 10 times (black), 5 times (blue), 2 times (green), control (yellow), 0.5 times (orange), 0.2 times (magenta), 0.1 times (red), larger than the control value in the original model (yellow). Please note that the dissociation constant Kd in panel (A) was set at in our original model while it was said to be in an experimental study [57].

doi: https://doi.org/10.1371/journal.pcbi.1000670.g013