In the present work we analyzed the profile of high voltage-activated (HVA) calcium (Ca 2+) currents in freshly isolated striatal medium spiny neurons (MSNs) from rodent models of both idiopathic and familial forms of Parkinson's disease (PD). MSNs were recorded from reserpine-treated and 6-hydroxydopamine (6-OHDA)-lesioned rats, and from DJ-1 and PINK1 (PTEN induced kinase 1) knockout ( -/-) mice. Our analysis showed no significant changes in total HVA Ca 2+ current. However, we recorded a net increase in the L-type fraction of HVA Ca 2+ current in dopamine-depleted rats, and of both N- and P-type components in DJ-1 -/- mice, whereas no significant change in Ca 2+ current profile was observed in PINK1 -/- mice. Dopamine modulates HVA Ca 2+ channels in MSNs, thus we also analyzed the effect of D1 and D2 receptor activation. The effect of the D1 receptor agonist SKF 83822 on Ca 2+ current was not significantly different among MSNs from control animals or PD models. However, in both dopamine-depleted rats and DJ-1 -/- mice the D2 receptor agonist quinpirole inhibited a greater fraction of HVA Ca 2+ current than in the respective controls. Conversely, in MSNs from PINK1 -/- mice we did not observe alterations in the effect of D2 receptor activation. Additionally, in both reserpine-treated and 6-OHDA-lesioned rats, the effect of quinpirole was occluded by the selective L-type Ca 2+ channel blocker nifedipine, while in DJ-1 -/- mice it was mostly occluded by ω-conotoxin GVIA, blocker of N-type channels. These results demonstrate that both dopamine depletion and DJ-1 deletion induce a rearrangement in the HVA Ca 2+ channel profile, specifically involving those channels that are selectively modulated by D2 receptors.
|Number of pages||12|
|Publication status||Published - Mar 17 2011|
- HVA calcium channels
- Medium spiny neuron
ASJC Scopus subject areas