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

Globus pallidus (GP) receives an abundant GABAergic (gamma-aminobutyric aci d) pathway from the corpus striatum. Several evidences suggested that alter ations of this pathway might underlie the development of movement disorders . Classical models on Parkinsonism are centred on the increased excitabilit y of GABAergic striatofugal neurons impinging GP and, therefore, on the pre sumed hypoactivity of GP neurons, but very few electrophysiological studies have addressed the activation of GABA receptors in mammalian GP. We have i solated 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 produc ed a large (greater than or equal to 35%) inhibition of calcium currents. T he GABA-induced inhibition of calcium currents strongly desensitized was mi micked by baclofen and prevented by hydroxy-saclofen, supporting the involv ement of GABA(B) receptors. The baclofen-mediated modulation was: (i) assoc iated with slowing of activation kinetics; (ii) relieved by prepulse facili tation; and (iii) G-protein-mediated. The response was slow in onset, requi ring the mobilization of intracellular cAMP, and was abolished by the combi nation of N-type and P-type calcium channel blockers. The GABA(B)-mediated effect, however, was confined to a particular subtype of GP neurons, identi fied by relatively small to medium soma. Differently, in cells characterize d by larger somata and capacitance, the baclofen response was negligible. I ntriguingly, these baclofen-resistant, larger neurons manifested a consiste nt low-voltage-activated (LVA) calcium current, not detected in baclofen-se nsitive cells, at least when recorded in whole-cell mode. This study demons trates 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 larg e modulation of high-voltage-activated (HVA) calcium currents, which may st rongly influence basal ganglia circuitry and partially explain some discrep ancies of classical models of extrapyramidal disorders.