MODULATION OF CALCIUM CURRENTS BY A D-1 DOPAMINERGIC PROTEIN-KINASE PHOSPHATASE CASCADE IN RAT NEOSTRIATAL NEURONS

In rat neostriatal neurons, D-1 dopamine receptors regulate the activity of cyclic AMP-dependent protein kinase (PKA) and protein phosphatase 1(PP1). The influence of these signaling elements on high voltage-activated (HVA) calcium currents was studied using whole-cell voltage-clamp techniques. The application of D-1 agonists or cyclic AMP analogs reversibly reduced N- and P-type Ca2+ currents. Inhibition of PKA antagonized this modulation, as did inhibition of PP1, suggesting that the D-1 effect was mediated by a PKA enhancement of PP1 activity directed toward Ca2+ channels. In a subset of neurons, D-1 receptor-mediated activation of PKA enhanced L-type currents. The differential regulation of HVA currents by the D-1 pathway helps to explain the diversity of effects this pathway has on synaptic integration and plasticity in medium spiny neurons.