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.

Stefani, A., Spadoni, F., Martorana, A., Lavaroni, F., Martella, G., Sancesario, G., et al. (2002). D2-mediated modulation of N-type calcium currents in rat globus pallidus neurons following dopamine denervation. EUROPEAN JOURNAL OF NEUROSCIENCE, 15(5), 815-825.

D2-mediated modulation of N-type calcium currents in rat globus pallidus neurons following dopamine denervation

STEFANI, ALESSANDRO;MARTORANA, ALESSANDRO;LAVARONI, FRANCO;MARTELLA, GIUSEPPINA;SANCESARIO, GIUSEPPE;BERNARDI, GIORGIO
2002-03-01

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.
mar-2002
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - NEUROLOGIA
English
Con Impact Factor ISI
Animals; Sympatholytics; Cyclic AMP; Calcium Channel Blockers; Tyrosine 3-Monooxygenase; Dopamine Agonists; Calcium Channels, N-Type; Rats; Receptors, Dopamine D2; Dopamine; Neurons; Neural Pathways; Rats, Wistar; Membrane Potentials; Substantia Nigra; Protein Kinase C; Calcium Signaling; Globus Pallidus; Male; Oxidopamine
Stefani, A., Spadoni, F., Martorana, A., Lavaroni, F., Martella, G., Sancesario, G., et al. (2002). D2-mediated modulation of N-type calcium currents in rat globus pallidus neurons following dopamine denervation. EUROPEAN JOURNAL OF NEUROSCIENCE, 15(5), 815-825.
Stefani, A; Spadoni, F; Martorana, A; Lavaroni, F; Martella, G; Sancesario, G; Bernardi, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/69149
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