QUALITATIVE-ANALYSIS OF MEMBRANE CURRENTS IN GLIAL-CELLS FROM NORMAL AND GLIOTIC TISSUE IN-SITU - DOWN-REGULATION OF NA-2 PURINERGIC RESPONSES( CURRENT AND LACK OF P)
R. Jabs et al., QUALITATIVE-ANALYSIS OF MEMBRANE CURRENTS IN GLIAL-CELLS FROM NORMAL AND GLIOTIC TISSUE IN-SITU - DOWN-REGULATION OF NA-2 PURINERGIC RESPONSES( CURRENT AND LACK OF P), Neuroscience, 81(3), 1997, pp. 847-860
To date, the electrophysiological properties of glial cells located in
reactive scar tissue are unknown. To address this issue two subtypes
of hippocampal glial cells, located in thin vital slices of normal or
gliotic brain tissue, were analysed for their voltage controlled ion c
hannels using the patch-clamp technique. Reactive gliosis was induced
in adult rats by a single peritoneal injection of kainic acid. The int
ensity of the following seizures was rated ascending from 1 to 6. Rats
which exhibited seizures of level 3 or higher showed, within three da
ys, a marked loss of pyramidal cells (60% in CA1 and CA3) and an incre
ase in the density of glial fibrillary acidic protein immunostaining,
representing an apparent increase in the number and size of astrocytes
in all layers of the hippocampal CAI subfield. Reactive and normal as
trocytes of one subtype, electrophysiologically characterized by time-
independent potassium currents, did not significantly differ in membra
ne potential and potassium conductivity. Glutamine synthetase-positive
, but mostly glial fibrillary acidic protein-negative, glial cells (pr
esumably representing immature astrocytes) were also included in this
study. This subtype of glial cells showed several voltage- and time-de
pendent potassium currents and, under control conditions, tetrodotoxin
-sensitive voltage-gated Na+ channels, which were almost completely lo
st after reactive gliosis. Another part of this study focuses on the s
ensitivity of reactive and control glial cells for extracellular ATP.
Several in vitro studies suggest that P-2 purinergic receptors on glia
l cells could trigger the induction of reactive gliosis. In contrast t
o results described on cultured astrocytes, we found in situ that hipp
ocampal glial cells were not sensitive to ATP or stable P-2 receptor a
gonists in control or in gliotic brain slices. In summary, the presenc
e of at least two different subtypes of hippocampal astrocytes was dem
onstrated for control as well as for gliotic brain tissue. A dramatic
down-regulation of tetrodotoxin-sensitive sodium channels in one subpo
pulation of reactive astrocytes was shown. This result supports the hy
pothesis that the presence of active neurons could be required to main
tain glial voltage-gated sodium channels. Furthermore, we conclude tha
t there is no longtime expression of P2 purinoceptors on hippocampal a
strocytes in situ, and therefore the involvement of astrocytic ATP rec
eptors in the genesis of reactive gliosis is unlikely. (C) 1997 IBRO.
Published by Elsevier Science Ltd.