The modulation of calcium current by GABA metabotropic receptors in a sub-population of pallidal neurons

Alessandro Stefani, Francesca Spadoni, P. Giacomini, F. Lavaroni, Giorgio Bernardi

Research output: Contribution to journalArticlepeer-review

Abstract

Globus pallidus (GP) receives an abundant GABAergic (γ-aminobutyric acid) pathway from the corpus striatum. Several evidences suggested that alterations of this pathway might underlie the development of movement disorders. Classical models on Parkinsonism are centred on the increased excitability of GABAergic striatofugal neurons impinging GP and, therefore, on the presumed hypoactivity of GP neurons, but very few electrophysiological studies have addressed the activation of GABA receptors in mammalian GP. We have isolated calcium currents in GP neurons dissociated from the adult rat brain and analysed GABA-mediated responses. In the presence of bicuculline, the fast, chloride-mediated, ionotropic responses were obscured and GABA produced a large (≥ 35%) inhibition of calcium currents. The GABA-induced inhibition of calcium currents strongly desensitized was mimicked by baclofen and prevented by hydroxy-saclofen, supporting the involvement of GABA(B) receptors. The baclofen-mediated modulation was: (i) associated with slowing of activation kinetics; (ii) relieved by prepulse facilitation; and (iii) G-protein-mediated. The response was slow in onset, requiring the mobilization of intracellular cAMP, and was abolished by the combination of N-type and P-type calcium channel blockers. The GABA(B)-mediated effect, however, was confined to a particular subtype of GP neurons, identified by relatively small to medium soma. Differently, in cells characterized by larger somata and capacitance, the baclofen response was negligible. Intriguingly, these baclofen-resistant, larger neurons manifested a consistent low-voltage-activated (LVA) calcium current, not detected in baclofen-sensitive cells, at least when recorded in whole-cell mode. This study demonstrates that GP neurons express functional GABA(A) and GABA(B) receptors. In a subset of GP neurons, the activation of GABA(B) receptors induces a large modulation of high-voltage-activated (HVA) calcium currents, which may strongly influence basal ganglia circuitry and partially explain some discrepancies of classical models of extrapyramidal disorders.

Original languageEnglish
Pages (from-to)3995-4005
Number of pages11
JournalEuropean Journal of Neuroscience
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 1999

Keywords

  • Baclofen
  • Basal ganglia
  • Movement disorders
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)

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