Hypoxic effects on
glutamate uptake and
ATP content in glial cells were investigated by using cultured C6
glioma cells. Mild regressive changes were found depending on the duration of the hypoxic insult, but
necrosis or detachment of the cells from the substratum was rarely observed.
Glutamate uptake was relatively well preserved after a short hypoxic insult, while a marked decrease in
glutamate uptake was observed after
hypoxia of long duration. The uptake of
sucrose was reduced in a similar pattern to
glutamate uptake. Hypoxic insult resulted in a significant reduction of the
ATP content in glial cells. Therefore, the decrease in
glutamate uptake by glial cells under
hypoxia is likely to be due to
ATP dependency, and not to the failure of a specific
glutamate uptake system, but the failure of a general uptake of the glial cells owing to the energy-dependent membrane dysfunction by
ATP depletion. These findings suggest that there are phased changes of astrocytic functions in a hypoxic condition, a preservative phase in the initial stages and then a dysfunctional phase in the later stages of
hypoxia.