+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

GABA transporter subtype 1 and GABA transporter subtype 3 modulate glutamatergic transmission via activation of presynaptic GABA(B) receptors in the rat globus pallidus



GABA transporter subtype 1 and GABA transporter subtype 3 modulate glutamatergic transmission via activation of presynaptic GABA(B) receptors in the rat globus pallidus



European Journal of Neuroscience 36(4): 2482-2492



The intra-pallidal application of γ-aminobutyric acid (GABA) transporter subtype 1 (GAT-1) or GABA transporter subtype 3 (GAT-3) transporter blockers [1-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid hydrochloride (SKF 89976A) or 1-[2-[tris(4-methoxyphenyl)methoxy]ethyl]-(S)-3-piperidinecarboxylic acid (SNAP 5114)] reduces the activity of pallidal neurons in monkey. This effect could be mediated through the activation of presynaptic GABA(B) heteroreceptors in glutamatergic terminals by GABA spillover following GABA transporter (GAT) blockade. To test this hypothesis, we applied the whole-cell recording technique to study the effects of SKF 89976A and SNAP 5114 on evoked excitatory postsynaptic currents (eEPSCs) in the presence of gabazine, a GABA(A) receptor antagonist, in rat globus pallidus slice preparations. Under the condition of postsynaptic GABA(B) receptor blockade by the intra-cellular application of N-(2,6-dimethylphenylcarbamoylmethyl)-triethylammonium bromide (OX314), bath application of SKF 89976A (10 μM) or SNAP 5114 (10 μM) decreased the amplitude of eEPSCs, without a significant effect on its holding current and whole cell input resistance. The inhibitory effect of GAT blockade on eEPSCs was blocked by (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl)phosphinic acid, a GABA(B) receptor antagonist. The paired-pulse ratio of eEPSCs was increased, whereas the frequency, but not the amplitude, of miniature excitatory postsynaptic currents was reduced in the presence of either GAT blocker, demonstrating a presynaptic effect. These results suggest that synaptically released GABA can inhibit glutamatergic transmission through the activation of presynaptic GABA(B) heteroreceptors following GAT-1 or GAT-3 blockade. In conclusion, our findings demonstrate that presynaptic GABA(B) heteroreceptors in putative glutamatergic subthalamic afferents to the globus pallidus are sensitive to increases in extracellular GABA induced by GAT inactivation, thereby suggesting that GAT blockade represents a potential mechanism by which overactive subthalamopallidal activity may be reduced in parkinsonism.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036409977

Download citation: RISBibTeXText

PMID: 22616751

DOI: 10.1111/j.1460-9568.2012.08147.x


Related references

Number, Density, and Surface/Cytoplasmic Distribution of Gaba Transporters at Presynaptic Structures of Knock-In Mice Carrying Gaba Transporter Subtype 1Green Fluorescent Protein Fusions. The Journal of Neuroscience 22(23): 10251-10266, 2002

Number, density, and surface/cytoplasmic distribution of GABA transporters at presynaptic structures of knock-in mice carrying GABA transporter subtype 1-green fluorescent protein fusions. Journal of Neuroscience 22(23): 10251-10266, 2002

gamma-Aminobutyric acid (GABA) signaling components in Drosophila: immunocytochemical localization of GABA(B) receptors in relation to the GABA(A) receptor subunit RDL and a vesicular GABA transporter. Journal of Comparative Neurology 505(1): 18-31, 2007

Veratridine- and glutamate-induced release of [3H]-GABA from cultured chick retina cells: possible involvement of a GAT-1-like subtype of GABA transporter. Brain Research 798(1-2): 217-222, 1998

The role of N-glycosylation in the stability, trafficking and GABA-uptake of GABA-transporter 1. Terminal N-glycans facilitate efficient GABA-uptake activity of the GABA transporter. Febs Journal 272(7): 1625-1638, 2005

Dopamine inhibits GABA transmission from the globus pallidus to the thalamic reticular nucleus via presynaptic D4 receptors. Neuroscience 169(4): 1672-1681, 2011

A functional role for both -aminobutyric acid (GABA) transporter-1 and GABA transporter-3 in the modulation of extracellular GABA and GABAergic tonic conductances in the rat hippocampus. Journal of Physiology 591(10): 2429-2441, 2013

A functional role for both GABA transporter-1 and GABA transporter-3 in the modulation of extracellular GABA and GABAergic tonic conductances in the rat hippocampus. 2013

Subtype-specific GABA transporter antagonists synergistically modulate phasic and tonic GABAA conductances in rat neocortex. Journal of Neurophysiology 94(3): 2073-2085, 2005

Synaptically released GABA activates both pre- and postsynaptic GABA(B) receptors in the rat globus pallidus. Journal of Neurophysiology 94(2): 1104-1114, 2005

Subsynaptic localization of GABA-A and GABA-B receptors in the monkey globus pallidus. Society for Neuroscience Abstracts 27(1): 764, 2001

Effects of GABA - A and GABA - B receptors stimulation on neuronal activity in the monkey globus pallidus. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 706 14, 2003

Synaptic and extrasynaptic GABA-A and GABA-B receptors in the globus pallidus: an electron microscopic immunogold analysis in monkeys. Neuroscience 131(4): 917-933, 2005

Effects of GABA-B receptor activation on glutamate and GABA release in the globus pallidus and subthalamic nucleus of monkey. Society for Neuroscience Abstracts 27(2): 2194, 2001

GABAergic modulation of the activity of globus pallidus neurons in primates: in vivo analysis of the functions of GABA receptors and GABA transporters. Journal of Neurophysiology 94(2): 990-1000, 2005