TY - JOUR
T1 - The modulation of calcium current by GABA metabotropic receptors in a sub-population of pallidal neurons
AU - Stefani, Alessandro
AU - Spadoni, Francesca
AU - Giacomini, P.
AU - Lavaroni, F.
AU - Bernardi, Giorgio
PY - 1999/11
Y1 - 1999/11
N2 - 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.
AB - 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.
KW - Baclofen
KW - Basal ganglia
KW - Movement disorders
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=0032697723&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032697723&partnerID=8YFLogxK
U2 - 10.1046/j.1460-9568.1999.00836.x
DO - 10.1046/j.1460-9568.1999.00836.x
M3 - Article
C2 - 10583488
AN - SCOPUS:0032697723
VL - 11
SP - 3995
EP - 4005
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
SN - 0953-816X
IS - 11
ER -