GAP-JUNCTIONS ARE REQUIRED FOR THE PROPAGATION OF SPREADING DEPRESSION

Spreading depression (SD) is a slowly propagating depression of cerebr al neuronal activity and transmembrane ionic gradients, that arises in response to a variety of noxious stimuli. SD bears a strong resemblan ce to gap junction-mediated calcium waves among cultured astrocytes. H ere, we show that gap junction-mediated intercellular diffusion is nec essary for the generation of SD. Waves of SD in the isolated chicken r etina were blocked by five different inhibitors of gap junctional coup ling, which was assessed by the intercellular transit of Lucifer Yello w (LY). Each of these gap junction blockers inhibited both the migrati on of SD and the diffusion of LY in a dose-dependent manner. In contra st, glutamate-evoked calcium influx into retinal cells was not affecte d by these compounds. The results indicate that intercellular coupling through gap junctions is required for SD. Gap junction-mediated commu nication might therefore constitute an important mechanism in both nor mative and pathological brain function. (C) 1995 John Wiley & Sons, In c.