Transient Calcium and Dopamine Increase PKA Activity and DARPP-32 Phosphorylation
Figure 5
Effect of Simultaneous, Transient Calcium and Dopamine Inputs
In all panels, the response to dopamine alone is shown with green dashed lines; the response to paired dopamine and calcium is shown with red solid lines.
(A) The cumulative increase in free PKAc following eight high-amplitude, brief dopamine pulses with 20-s intervals, is enhanced when a high-amplitude, brief calcium input is paired with each dopamine pulse.
(B) Phosphorylation of Thr34 is enhanced when calcium and dopamine inputs are paired.
(C) PP1 inhibition is more pronounced when calcium and dopamine inputs are paired due to the increase in phosphoThr34.
(D) The ratio of PKAc to PP1 is enhanced when calcium and dopamine inputs are paired.
(E) Some dephosphorylation on Thr75 occurs following a dopamine input due to the PKA dependent activation of PP2A. When in addition calcium is transiently elevated, calcium-dependent activation of PP2A significantly decreases phosphoThr75.
(F) The total formation of activated PKA (both free and bound to phosphoThr75) is larger with dopamine inputs alone. This is partly due to the calcium-dependent decrease in the cAMP formation, but also the PKAc interaction with phosphoThr75 is important.