title: 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.
abstract: In the present work we analyzed the profile of high voltage-activated (HVA) calcium (Ca2+) 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 Ca2+ current. However, we recorded a net increase in the L-type fraction of HVA Ca2+ current in dopamine-depleted rats, and of both N- and P-type components in DJ-1-/- mice, whereas no significant change in Ca2+ current profile was observed in PINK1-/- mice. Dopamine modulates HVA Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ channel profile, specifically involving those channels that are selectively modulated by D2 receptors.
authors.affiliation: Department of Neuroscience, University Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Martella
authors.forename: G
authors.initials: G
authors.lastname: Madeo
authors.forename: T
authors.initials: T
authors.lastname: Schirinzi
authors.forename: A
authors.initials: A
authors.lastname: Tassone
authors.forename: G
authors.initials: G
authors.lastname: Sciamanna
authors.forename: F
authors.initials: F
authors.lastname: Spadoni
authors.forename: A
authors.initials: A
authors.lastname: Stefani
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.forename: A
authors.initials: A
authors.lastname: Pisani
authors.forename: P
authors.initials: P
authors.lastname: Bonsi
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics*; D009924:Organ Culture Techniques; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000172:deficiency / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D015513:Oncogene Proteins; D017448:Receptors, Dopamine D2; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D004298:Dopamine