GLUTAMATE BLOCKS ASTROGLIAL STELLATION - EFFECT OF GLUTAMATE UPTAKE AND VOLUME CHANGES

Neurotransmitters which increase intracellular cAMP levels can cause c ultured astroglia to change from a flat, polygonal shape to a stellate morphology. Little is known about how glial stellation can be regulat ed by other transmitters. In the present study, we demonstrated that L -glutamate blocked isoproterenol(ISO) or dibutyryl-cAMP induced stella tion in astroglia. The glutamate inhibition was concentration dependen t, with its maximal effect on > 90% of cells at 500 mu M. Glutamate al so reversed glial stellation within a short period (< 30 min). Glutama te uptake analogues, D-glutamate and D-aspartate, rather than receptor agonists, kainate and quisqualate, mimicked the glutamate effect. Lik ewise, the glutamate uptake blocker, D-thero-beta-hydroxyaspartate, bl ocked the glutamate effect. The glutamate inhibition was not a result of inhibition of cAMP formation, since norepinephrine, which inhibited 80% of ISO-stimulated cAMP, also caused glial stellation. Increases i n extracellular K+ to 50 mM also reduced glial stellation, whereas 25 mM K+ had little effect. Since 25 mM K+ caused much greater depolariza tion than 400 mu M glutamate, it was unlikely that the effects of both glutamate and high [K+] on glial stellation were due to membrane depo larization. Hypotonic treatment (120 mOsm) enhanced, whereas hypertoni c treatment (520 mOsm) prevented, the glutamate reversal of glial stel lation. Thus, glial swelling appeared to be a primary mechanism for th e inhibitory effect of glutamate and high [K+] on glial stellation. Th is mechanism could also explain the observation that glutamate inhibit ed stellation induced by PMA, a PKC activator. Our data suggest that g lutamate released from neurons during neuronal activity or pathology c an be taken up by astrocytes and alter their morphology. Changes in gl ial morphology may in turn affect the volume and composition of the ex tracellular space and, as a result, neuronal activity. (C) 1994 Wiley- Liss, Inc.