Increased calcium/calmodulin protein kinase activity in astrocytes chronically exposed to ethanol: influences on glutamate transport.

The effects of ethanol exposures on calcium/calmodulin-dependent protein kinase activity as well as its influence on glutamate uptake were determined in astrocytes prepared from neonatal rat cerebral cortex. Acute 15-min exposure to 100 mM ethanol had no effect on Ca2+/CaM-dependent protein kinase activity. However, chronic exposure to 100 mM ethanol for 4 days elicited a significant increase in the activity of this enzyme with no parallel increase in its expression. Ca2+/CaM-independent kinase activity was less than 1% of the Ca2+/CaM-dependent kinase activity and was unaffected by any of the ethanol exposures. Exposure to 100 mM ethanol for four days also resulted in a significant increase in Na+-dependent [3H]glutamate uptake which was reversed when ethanol-exposed astrocytes were co-incubated with KN-93, a specific inhibitor of Ca2+/CaM kinase. These results suggest that the effects of ethanol on glutamate transport may be mediated in part, by the level of Ca2+/CaM kinase activity.