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- Title
Functional GABA[sub A] receptors on human glioma cells.
- Authors
Labrakakis, Charalampos; Patt, Stephan; Hartmann, Jana; Kettenmann, Helmut
- Abstract
Glioma cells in acute slices and in primary culture, and glioma-derived human cell lines were screened for the presence of functional GABA[sub A] receptors. Currents were measured in whole-cell voltage clamp in response to γ-aminobutyric acid (GABA). While cells from the most malignant glioma, the glioblastoma multiforme, did not respond to GABA, an inward current (under our experimental conditions with high Cl[sup -] concentration in the pipette) was induced in gliomas of lower grades, namely in 71% of oligodendroglioma cells and in 62% of the astrocytoma cells. Glioma cell lines did not express functional GABA[sub A] receptors, irrespective of the malignancy of the tumour they originate from. The currents elicited by application of GABA were due to activation of GABA[sub A] receptors; the specific agonist muscimol mimicked the response, the antagonists bicuculline and picrotoxin blocked the GABA-activated current and the benzodiazepine receptor agonist flunitrazepam augmented the GABA-induced current and the benzodiazepine inverse agonist DMCM decreased the GABA current. Cells were heterogeneous with respect to the direction of the current flow as tested in gramicidin perforated patches: in some cells GABA hyperpolarized the membrane, while in the majority it triggered a depolarization. Moreover, GABA triggered an increase in [Ca[sup 2+]][sub i] in the majority of the tumour cells due to the activation of Ca[sup 2+] channels. Our results suggest a link between the expression of GABA receptors and the growth of glioma cells as the disappearance of functional GABA[sub A] receptors parallels unlimited growth typical for malignant tumours and immortal cell lines.
- Subjects
GABA receptors; GLIOMAS; CALCIUM channels
- Publication
European Journal of Neuroscience, 1998, Vol 10, Issue 1
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1046/j.1460-9568.1998.00036.x