Intercellular Diffusional Coupling between Glial Cells in Slices from the Striatum

Abstract

In the central nervous system (CNS), macroglial cells (astrocytes and oligodendrocytes) represent the main cell population coupled by gap junctions. Indeed, a much higher level of gap junctional communication is observed in macroglial cells than in neurons and this communication process persists up to the adult stage in these cells (1). Gap junctions are characterized by clusters of intercellular channels connecting the cytoplasm of adjacent cells. These channels are constituted by two hemichannels, the connexons, each of them being formed by six structural subunit proteins, the connexins (Cxs). Cxs are organized around a relatively large hydrated pore which allows the diffusion of ions and small molecules up to 1–1.2 kDa, providing thus the morphological basis for electrical and metabolic coupling (2). Although Cxs are expressed in neurons as well as in glial and ependymal cells (3), glial cells and astrocytes, particularly, contain the highest level of Cxs from the late embryo to the adult (4). Cx43, which is prevalent in astrocytes, is detected early during development, peaks at birth, and remains constant throughout the adult life (4). Cx30 is also found in mature astrocytes and its distribution resembles that of Cx43 (5). Experiments performed with low molecular weight tracers (Lucifer yellow, biocytin, neurobiotin) have indicated that populations of 10 to 100 astrocytes can communicate through gap junction channels in either cortical, hippocampal, or cerebellar slices (6–8). However, although Cx43 was also detected in striatal astrocytes, as reported in a previous study, the intercellular diffusion of the low molecular weight fluorescent dye Lucifer yellow was not detected in astrocytes injected with this dye in striatal slices (9,10).This is surprising because functional studies performed on astrocytic primary cultures from different brain structures, including the striatum, have demonstrated that these cells are highly coupled by gap junction channels (3,11).A marked regional heterogeneity was found in these cell culture studies (12,13) but astrocytes from either the cerebral cortex, the hippocampus, the brain stem, the cerebellum or the striatum were all shown to express Cx43 and to exchange fluorescent dyes, calcium signaling molecules, glucose, and glutamate (14).