EXPRESSION OF VOLTAGE-ACTIVATED CHLORIDE CURRENTS IN ACUTE SLICES OF HUMAN GLIOMAS

Using whole-cell patch-clamp recordings, we identified a novel voltage -activated chloride current that was selectively expressed in glioma c ells from 23 patient biopsies. Chloride currents were identified in 64 % of glioma cells studied in acute slices of nine patient biopsies. Th ese derived from gliomas of various pathological grades. In addition, 98% of cells acutely isolated or in short-term culture from 23 patient s diagnosed with gliomas showed chloride current expression. These cur rents, which we termed glioma chloride currents activated at potential s >45 mV, showed pronounced outward rectification, and were sensitive to bath application of the presumed Cl- channel specific peptide chlor otoxin (similar to 600 nM) derived from Leiurus scorpion venom. Intere stingly, low grade tumours (e.g., pilocytic astrocytomas), containing more differentiated, astrocyte-like cells showed expression of glioma chloride currents in concert with voltage-activated sodium and potassi um currents also seen in normal astrocytes. By contrast, high grade tu mours (e.g., glioblastoma multiforme) expressed almost exclusively chl oride currents, suggesting a gradual loss of Na+ currents and gain of Cl- currents with increasing pathological tumour grade. To expand on t he observation that these chloride currents nts are glioma-specific, w e introduced experimental rumours in scid mice by intracranial injecti on of D54MG glioma cells and subsequently recorded from tumour cells a nd adjacent normal glial cells in acute slices. We consistently observ ed expression of chlorotoxin-sensitive chloride channels in implanted glioma cells, bur without evidence for expression of chloride channels in surrounding ''normal'' host glial cells, suggesting that these chl oride channels are probably a glioma-specific feature. Finding of this novel glioma specific Cl- channel in gliomas in situ and it's selecti ve binding of chlorotoxin may provide a way to identify or target glio ma cells in the future. (C) 1998 IBRO. Published by Elsevier Science L td.