Premium
GAT‐1 regulates both tonic and phasic GABA A receptor‐mediated inhibition in the cerebral cortex
Author(s) -
Bragina Luca,
Marchionni Ivan,
Omrani Azar,
Cozzi Andrea,
PellegriniGiampietro Domenico E.,
Cherubini Enrico,
Conti Fiorenzo
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05273.x
Subject(s) - inhibitory postsynaptic potential , tonic (physiology) , gabaergic , glutamate receptor , neocortex , gamma aminobutyric acid , gabaa receptor , chemistry , extracellular , stimulation , microdialysis , cerebral cortex , neuroscience , medicine , endocrinology , biology , receptor , biochemistry
γ‐Aminobutyric acid 1 (GAT‐1) is the most copiously expressed GABA transporter; we studied its role in phasic and tonic inhibition in the neocortex using GAT‐1 knockout (KO) mice. Immunoblotting and immunocytochemical studies showed that GAT‐2 and GAT‐3 levels in KOs were unchanged and that GAT‐3 was not redistributed in KOs. Moreover, the expression of GAD65/67 was increased, whereas that of GABA or VGAT was unchanged. Microdialysis studies showed that in KOs spontaneous extracellular release of GABA and glutamate was comparable in WT and KO mice, whereas KCl‐evoked output of GABA, but not of glutamate, was significantly increased in KOs. Recordings from layer II/III pyramids revealed a significant increase in GABA A R‐mediated tonic conductance in KO mice. The frequency, amplitude and kinetics of spontaneous inhibitory post‐synaptic currents (IPSCs) were unchanged, whereas the decay time of evoked IPSCs was significantly prolonged in KO mice. In KO mice, high frequency stimulation of GABAergic terminals induced large GABA A R‐mediated inward currents associated with a reduction in amplitude and decay time of IPSCs evoked immediately after the train. The recovery process was slower in KO than in WT mice. These studies show that in the cerebral cortex of GAT‐1 KO mice GAT‐3 is not redistributed and GADs are adaptively changed and indicate that GAT‐1 has a prominent role in both tonic and phasic GABA A R‐mediated inhibition, in particular during sustained neuronal activity.