Transient treatments with L-glutamate and threo-β-hydroxyaspartate induce swelling of rat cultured astrocytes

We characterized swelling of rat cultured astrocytes induced by L-glutamate and its analogues. Among L-glutamate receptor agonists, L-glutamate, L-aspartate, L-cysteic acid, DL-homocysteic acid, quisqualate and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) increased astrocytic intracellular volume (H-3-OMG space), while kainate, and N-methyl-D-aspartate did not. Threo-beta-hydroxyaspartate (TBHA), D-aspartate and L-trans-pyrrolidine-2,4-dicarboxylic acid, high-affinity substrates for Na+-dependent L-glutamate transporters, increased astrocytic H-3-OMG space. L-Glutamate (0.5 mM) increased astrocytic H-3-OMG space to 300% of control in 40-60 min. The increase in 3H-OMG space by 1 mM TBHA was comparable to the L-glutamate-induced one. After a 10 min-exposure to 0.5 mM L-glutamate, astrocytic H-3-OMG space was further increased to 200% even in the absence of L-glutamate. Astrocytes transiently exposed to L-glutamate did not increase their cell volume in K+-free medium and in the presence of 1 mM ouabain, a Na+-K(+)ATPase inhibitor. The increase after a transient exposure was also observed by a treatment of 1 mM TBHA, but not by 0.5 mM quisqualate. These results suggest that the volume increases after a transient treatment are mediated by activation of Na+-dependent L-glutamate transporter. (C) 2000 Elsevier Science Ltd. All rights reserved.