A reconfiguration of CaV2 Ca2+ channel current and its dopaminergic D2 modulation in developing neostriatal neurons

The modulatory effect of D(2) dopamine receptor activation on calcium currents was studied in neostriatal projection neurons at two stages of rat development: postnatal day (PD)14 and PD40. D(2)-class receptor agonists reduced whole cell calcium currents by about 35% at both stages, and this effect was blocked by the D(2) receptor antagonist sulpiride. Nitrendipine partially occluded this modulation at both stages, indicating that modulation of Ca(V)1 channels was present throughout this developmental interval. Nevertheless, modulation of Ca(V)1 channels was significantly larger in PD40 neurons. omega-Conotoxin GVIA occluded most of the Ca(2+) current modulation in PD14 neurons. However, this occlusion was greatly decreased in PD40 neurons. omega-Agatoxin TK occluded a great part of the modulation in PD40 neurons but had a negligible effect in PD14 neurons. The data indicate that dopaminergic D(2)-mediated modulation undergoes a change in target during development: from Ca(V)2.2 to Ca(V)2.1 Ca(2+) channels. This change occurred while Ca(V)2.2 channels were being down-regulated and Ca(V)2.1 channels were being up-regulated. Presynaptic modulation mediated by D(2) receptors reflected these changes; Ca(V)2.2 type channels were used for release in young animals but very little in mature animals, suggesting that changes took place simultaneously at the somatodendritic and the synaptic membranes.