Transient Calcium and Dopamine Increase PKA Activity and DARPP-32 Phosphorylation
Figure 2
Model Response to Either D1 Activation or Calcium Elevation
Dopamine elevation at time 300 s (A3) leads to a nine times increase in phosphoThr34 within 2 min (A1, solid line), while phosphoThr75 is reduced to 60% of control (A2, solid line). This is quantitatively in accordance with experimental results. The PKA-dependent activation of PP2A is critical for this behavior; if left out of the model, phosphoThr75 increases instead of decreases (blue dashed line). Calcium-dependent activation of PP2A is not critical to simulate the correct response to D1 activation (purple dotted line). Calcium elevation at time 300 s (B3) leads to a reduction in both Thr34 (B1, solid line) and Thr75 phosphorylation (B2, solid line). In contrast to the result in A1 and A2, this response requires calcium-dependent activation of PP2A; if left out of the model (purple dotted line), calcium causes an increase in Thr75 phosphorylation.