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

G. Martella, G. Madeo, T. Schirinzi, A. Tassone, G. Sciamanna, F. Spadoni, A. Stefani, J. Shen, A. Pisani, P. Bonsi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)240-251
Number of pages12
JournalNeuroscience
Volume177
DOIs
Publication statusPublished - Mar 17 2011

Keywords

  • 6-hydroxydopamine
  • DJ-1
  • HVA calcium channels
  • Medium spiny neuron
  • PINK1
  • Reserpine

ASJC Scopus subject areas

  • Neuroscience(all)

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