ASTROGLIAL GAP JUNCTION COMMUNICATION IS INCREASED BY TREATMENT WITH EITHER GLUTAMATE OR HIGH K+ CONCENTRATION

Astroglia are extensively coupled by gap junctions and form a function al syncytium. Astroglial gap junctions are thought to be involved in t he spatial buffering of K+ in vivo and in the Ca2+ waves seen on gluta mate receptor activation. The conductivity of gap junctions is regulat ed by several second messengers, with up-regulation by cyclic AMP and down-regulation through activation of protein kinase C, decreases in i ntracellular pH, or increases in the free cytosolic Ca2+ concentration . The results presented here indicate that dye coupling of astroglia i s significantly up-regulated by membrane depolarization, both by incre ases in the extracellular K+ concentration and directly by ionophores. Furthermore, glutamate, kainate, and quisqualate, which depolarize as troglial cells through activation of ionotropic receptors, also increa se dye coupling in astroglia. The effect of kainate and quisqualate wa s reversed by 6-cyano-7-nitroquinoxaline-2,3-dione, an inhibitor of th e ionotropic glutamate receptor. A dose-dependent decrease in dye coup ling was seen when the cells were injected with increasing concentrati ons of Ca2+. However, if the cells were simultaneously depolarized, th e inhibitory effect of Ca2+ on gap junctional conductance was reversed . Significant increases over basal coupling was attained when the cell s were injected with Ca2+ if they were treated with kainate or Kf. The se data suggest that ligands that depolarize astroglia enhance gap jun ction communication between astroglia and that this enhancement may be important in maintaining communication between astroglia in the face of elevated Ca2+ levels.