ASTROCYTIC SWELLING DUE TO HYPOTONIC OR HIGH K+ MEDIUM CAUSES INHIBITION OF GLUTAMATE AND ASPARTATE UPTAKE AND INCREASES THEIR RELEASE

Astrocytic swelling occurs readily in ischemia and traumatic brain inj ury (TBI) as part of the cytotoxic or cellular edema response. Ischemi a is known to produce large extracellular increases in both [K+] and e xcitatory amino acids (EAA) in vivo, and astrocytic swelling in vitro leads to marked release of EAA. In this study we compared the effect o f swelling due to hypotonic media and high K+ medium on the uptake and release of EAA by rat primary astrocyte cultures in vitro. In both ca ses, there was a significant inhibition of uptake of [H-3]L-glutamate and [H-3]D-aspartate, and increased release of preloaded [H-3]D-aspart ate, The kinetics of the increased efflux was very different in respon se to hypotonic or high K+ media. In hypotonic medium there was a rapi d initial release followed by a decline in the rate of release over ti me. This release was independent of whether Na+ was present. Upon expo sure to high K+ medium there was a slow progressive increase in releas e of [H-3]D-aspartate, which never showed any subsequent decline until the media was returned to normal [K+]. In high K+ media there was als o an initial transient increase in [H-3]D-aspartate release, which we attribute to reversal of the amino acid uptake system. The increased r elease due to hypotonic medium was not affected by a drop in temperatu re from 37 to 26 degrees C, while the increased release due to high K medium was completely inhibited. The decreased uptake and increased r elease of EAA when astrocytes swell will short-circuit a presumed impo rtant, protective uptake system for EAA and may contribute to the incr eased levels of extracellular EAA seen during ischemia, TBI, and other pathologic states.