FUNCTIONAL GABA(A) RECEPTORS ON HUMAN GLIOMA-CELLS

Glioma cells in acute slices and in primary culture, and glioma-derive d human cell lines were screened for the presence of functional GABA(A ) receptors. Currents were measured in whole-cell voltage clamp in res ponse to gamma-aminobutyric acid (GABA). While cells from the most mal ignant glioma, the glioblastoma multiforme, did not respond to GABA, a n inward current (under our experimental conditions with high Cl- conc entration in the pipette) was induced in gliomas of lower grades, name ly in 71% of oligodendroglioma cells and in 62% of the astrocytoma cel ls, Glioma cell lines did not express functional GABA(A) receptors, ir respective of the malignancy of the tumour they originate from. The cu rrents elicited by application of GABA were due to activation of GABA( A) receptors; the specific agonist muscimol mimicked the response, the antagonists bicuculline and picrotoxin blocked the GABA-activated cur rent and the benzodiazepine receptor agonist flunitrazepam augmented t he GABA-induced current and the benzodiazepine inverse agonist DMCM de creased the GABA current. Cells were heterogeneous with respect to the direction of the current flow as tested in gramicidin perforated patc hes: in some cells GABA hyperpolarized the membrane, while in the majo rity it triggered a depolarization. Moreover, GABA triggered an increa se in [Ca2+](i) in the majority of the tumour cells due to the activat ion of Ca2+ channels, Our results suggest a link between the expressio n of GABA receptors and the growth of glioma cells as the disappearanc e of functional GABA(A) receptors parallels unlimited growth typical f or malignant tumours and immortal cell lines.