ALTERED PROFILE AND D2-DOPAMINE RECEPTOR MODULATION OF HIGH VOLTAGE-ACTIVATED CALCIUM CURRENT IN STRIATAL MEDIUM SPINY NEURONS FROM ANIMAL MODELS OF PARKINSON'S DISEASE

作者：Martella G; Madeo G; Schirinzi T; Tassone A; Sciamanna G; Spadoni F; Stefani A; Shen J; Pisani A^*; Bonsi P

来源：Neuroscience, 2011, 177: 240-251.

DOI：10.1016/j.neuroscience.2010.12.057

• HVA calcium channels
• medium spiny neuron
• 6-hydroxydopamine
• reserpine
• DJ-1
• PINK1

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 omega-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.

• 出版日期2011-3-17