Transient Calcium and Dopamine Increase PKA Activity and DARPP-32 Phosphorylation
Figure 4
Responses to Transient Dopamine and Calcium Elevations
(A1) A brief, high-amplitude (solid line), or slow, low-amplitude (dashed line) dopamine elevation, with approximately equal area under the curve, is used as input to the model network. Dopamine produces an elevation in cAMP (A2), an elevation in PKAc (A3), and an increase in phosphoThr34 (A4). While the cAMP signal follows the dynamics of the dopamine signal, PKAc formation and Thr34 phosphorylation are proportional to total amount of dopamine, as if integrating the cAMP signal because these reactions occur on a slower time scale.
(B1) A fast (solid line) or slow (dashed line) transient calcium signal is used as input to the model. Calcium produces a decrease in cAMP (B2) due to both calcium-dependent activation of PDE1 as well as calcium-dependent inhibition of AC5. PDE1 has a larger effect on the maximal cAMP decrease, whereas AC5 has a larger effect on the later part of the cAMP reduction. Despite a decrease in cAMP, the free PKAc concentration (B3, solid line) is transiently increased following a fast and high calcium input, due to the calcium-dependent activation of PP2A, and causes an increase in phosphoThr34 (B4, solid line). A slower calcium input has minor effects on PKAc (B3, dashed line), but causes an initial decrease in phosphoThr34 (B4, dashed line), mostly due to a prolonged activation of PP2B.