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.