Astrocytic Swelling Due to Hypotonic or High K⁺Medium Causes Inhibition of Glutamate and Aspartate Uptake and Increases Their Release

Abstract

Summary: Astrocytic swelling occurs readily in ischemia and traumatic brain injury (TBI) as part of the cytotoxic or cellular edema response. Ischemia is known to pro duce large extracellular increases in both [K + 1 and excit atory amino acids (EAA) in vivo, and astrocytic swelling in vitro leads to marked release of EAA. In this study we compared the effect of 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 cases, there was a significant inhibition of uptake of [3HlL glutamate and [3Hln-aspartate, and increased release of preloaded eHln-aspartate. The kinetics of the increased efflux was very different in response to hypotonic or high K + media. In hypotonic medium there was a rapid initial release followed by a decline in the rate of release over time. This release was independent of whether Na + was present. Upon exposure to high K + medium there was a Marked astrocyte swelling is a prominent occur rence during and after ischemia (Ames et aI. , 1968; Garcia et aI. , 1977; Kalimo et aI. , 1977; Jenkins et aI., 1979 Jenkins et aI., , 1982Garcia 1984; Kimelberg and Ran som, 1986;Kraig and Petito, 1989;Hatashita and Hoff, 1990; Chen et aI. , 1992; Siesjo, 1992). In order to study the consequences and mechanisms of such swelling we have used primary astrocyte cultures swollen by hypotonic or high K + solutions as model systems (Walz 1987; O'Connor et ai. , 1992). We and others have observed that exposure to such solu tions will release endogenous or preloaded radiola beled taurine, glutamate, or aspartate, and this ef-

The Protein Kinase C Activator Phorbol Myristate Acetate Decreases Brain Edema by Aquaporin 4 Downregulation after Middle Cerebral Artery Occlusion in the Rat

“…Different mechanisms have been proposed to explain the origins of the brain edema that occurs during the early stages post-ischemia, but this issue remains unresolved (Chen and Swanson, 2003;Kimelberg et al, 1995). To the best of our knowledge, we demonstrate here for the first time that the intravenous infusion of PMA reduces brain water content and the resulting shift of electrolytes in a rat model of MCA occlusion.…”

Glutamate Released from Glial Cells Synchronizes Neuronal Activity in the Hippocampus

“…Astrocytes can release glutamate through different mechanisms, including a calcium-dependent, possibly vesicular, form of release (Parpura et al, 1994;Pasti et al, 1997Pasti et al, , 2001Araque et al, 1998aAraque et al, , 2000Bezzi et al, 1998Bezzi et al, , 2004Parpura and Haydon, 2000), the reverse operation of glutamate transporters (Nicholls and Attwell, 1990;Longuemare and Swanson, 1995), the opening of large pore channels (Kimelberg et al, 1990(Kimelberg et al, , 1995Duan et al, 2003;Ye et al, 2003), and the activity of the cystine-glutamate antiporter (Pow, 2001;Baker et al, 2002). Our present study did not aim at identifying the actual mechanism by which astrocytes release glutamate.…”

Inhibition of glutamate uptake by a polypeptide toxin (phoneutriatoxin 3-4) from the spider Phoneutria nigriventer

“…65 %, in comparison with the 15 % inhibition in Ca# + -free medium ( Figure 3A). Thus, because veratridine depolarizes the membrane via a mechanism distinct from that of KCl, an artifact related to the conditions produced by depolarization with KCl, such as swelling [35], was less probable.…”