title: D2-mediated modulation of N-type calcium currents in rat globus pallidus neurons following dopamine denervation.
abstract: We have studied the effects of dopamine and the D2-like agonist quinpirole on calcium currents of neurons isolated from the striatum and the globus pallidus (GP). Experiments were performed in young adult rats, either in control conditions or following lesion of the nigrostriatal pathway by the unilateral injection of 6-hydroxydopamine (6-OHDA) in the substantia nigra. Apomorphine-driven contralateral turning, 15 days after lesioning, assessed the severity of the dopamine denervation. In addition, the loss of tyrosine hydroxylase immunohistochemistry confirmed the extent of the toxin-induced damage. In both striatal medium spiny (MS) and GP neurons of control animals dopamine and quinpirole promoted a very modest inhibition of calcium conductance. Following 6-OHDA, the inhibition was unaltered in MS (from 10 to 12%), but significantly augmented in GP neurons (21% vs. 9%). Interestingly, analogous inhibition was observed in GP neurons dissociated 20 h after reserpine treatment. Further features of the D2 response were thus studied only in neurons isolated from 6-OHDA-lesioned GP. The D2 modulation was G-protein-mediated but not strictly voltage-dependent. omega-Conotoxin-GVIA occluded the response implying the involvement of N-type calcium channels. The effect of quinpirole developed fast and was insensitive to alterations of cytosolic cAMP. The incubation in phorbol esters or OAG blocked the D2 effect, supporting the involvement of PKC. These findings suggest that postsynaptic D2-like receptors are functionally expressed on GP cell bodies and may supersensitize following dopamine-denervation. A direct D2 modulation of calcium conductance in GP may alter GP firing properties and GABA release onto pallidofugal targets.
authors.affiliation: IRCCS Fondazione Santa Lucia, Via Ardeatina 306, 00179 Roma, Italy. stefani@uniroma2.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
authors.forename: Francesca
authors.initials: F
authors.lastname: Spadoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
authors.forename: Franco
authors.initials: F
authors.lastname: Lavaroni
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Martella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sancesario
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013565:Sympatholytics / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; D016627:Oxidopamine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C; D004298:Dopamine