[en] Media conditioned by cultured neonatal cerebral cortex microexplants (CCM) or astrocytes (ACM) contain low molecular weight (< 1,000 Da) substance(s) which inhibits the gamma aminobutyric acid (GABA)-induced inward current recorded in cerebellar granule cells and hippocampal neurons in culture using the whole-cell patch-clamp technique. This effect is specific for CCM and ACM, as medium conditioned by PC12 cells (PC12CM) does not affect the GABA response of these cells. It is also specific for GABA-induced currents because glutamate-induced currents do not change either in amplitude or in shape in the presence of CCM or ACM. The inhibitory effect on the GABA response in cerebellar granule cells of both ACM and CCM could be suppressed by flumazenil, a specific benzodiazepine (BZD) antagonist and could be mimicked by two BZD inverse agonists. These data thus demonstrate the presence of a BZD inverse agonist-like activity in CCM and ACM. This effect of ACM on different neuronal cell types was heterogenous since no detectable effect could be observed on the GABA-induced current in GABA-responsive dorsal root ganglion (DRG) neurons, presumably reflecting a functional heterogeneity of the GABAA receptors present in these different neuronal subsets. By the release of such an endogenous BZD inverse agonist-like activity, glia cells could possibly modulate GABAA receptor-mediated responses.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Rigo, Jean-Michel; Université de Liège - ULiège > CNCM
Belachew, Shibeshih ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie
Leprince, Pierre ; Université de Liège - ULiège > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc.
Malgrange, Brigitte ; Université de Liège - ULiège > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc.
Rogister, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
Kettenmann, H.
Moonen, Gustave ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie - Doyen de la Faculté de Médecine
Language :
English
Title :
Astroglia-Released Factor Shows Similar Effects as Benzodiazepine Inverse Agonists
Publication date :
01 November 1994
Journal title :
Journal of Neuroscience Research
ISSN :
0360-4012
eISSN :
1097-4547
Publisher :
John Wiley & Sons, Hoboken, United States - New York
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