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Glial glutamate transporter and glutamine synthetase regulate GABAergic synaptic strength in the spinal dorsal horn
Author(s) -
Jiang Enshe,
Yan Xisheng,
Weng HanRong
Publication year - 2012
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.1471-4159.2012.07694.x
Subject(s) - gabaergic , glutamate receptor , neuroscience , disinhibition , glutamine synthetase , biology , gamma aminobutyric acid , inhibitory postsynaptic potential , glutamine , biochemistry , receptor , amino acid
J. Neurochem. (2012) 121 , 526–536. Abstract Decreased GABAergic synaptic strength (‘disinhibition’) in the spinal dorsal horn is a crucial mechanism contributing to the development and maintenance of pathological pain. However, mechanisms leading to disinhibition in the spinal dorsal horn remain elusive. We investigated the role of glial glutamate transporters (GLT‐1 and GLAST) and glutamine synthetase in maintaining GABAergic synaptic activity in the spinal dorsal horn. Electrically evoked GABAergic inhibitory post‐synaptic currents (eIPSCs), spontaneous IPSCs (sIPSCs) and miniature IPSCs were recorded in superficial spinal dorsal horn neurons of spinal slices from young adult rats. We used (2 S ,3 S )‐3‐[3‐[4‐(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB‐TBOA), to block both GLT‐1 and GLAST and dihydrokainic acid to block only GLT‐1. We found that blockade of both GLAST and GLT‐1 and blockade of only GLT‐1 in the spinal dorsal horn decreased the amplitude of GABAergic eIPSCs, as well as both the amplitude and frequency of GABAergic sIPSCs or miniature IPSCs. Pharmacological inhibition of glial glutamine synthetase had similar effects on both GABAergic eIPSCs and sIPSCs. We provided evidence demonstrating that the reduction in GABAergic strength induced by the inhibition of glial glutamate transporters is due to insufficient GABA synthesis through the glutamate–glutamine cycle between astrocytes and neurons. Thus, our results indicate that deficient glial glutamate transporters and glutamine synthetase significantly attenuate GABAergic synaptic strength in the spinal dorsal horn, which may be a crucial synaptic mechanism underlying glial–neuronal interactions caused by dysfunctional astrocytes in pathological pain conditions.