Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons

The transmembrane connexin proteins of gap junctions link extracellularly t o form channels for cell-to-cell exchange of ions and small molecules. Two primary hypotheses of gap junction coupling in the CNS are the following: ( 1) generalized coupling occurs between neurons and glia, with some connexin s expressed in both neurons and glia, and (2) intercellular junctional coup ling is restricted to specific coupling partners, with different connexins expressed in each cell type. There is consensus that gap junctions link neu rons to neurons and astrocytes to oligodendrocytes, ependymocytes, and othe r astrocytes. However, unresolved are the existence and degree to which gap junctions occur between oligodendrocytes, between oligodendrocytes and neu rons, and between astrocytes and neurons. Using light microscopic immunocyt ochemistry and freeze-fracture replica immunogold labeling of adult rat CNS , we investigated whether four of the best-characterized CNS connexins are each present in one or more cell types, whether oligodendrocytes also share gap junctions with other oligodendrocytes or with neurons, and whether ast rocytes share gap junctions with neurons. Connexin32 (Cx32) was found only in gap junctions of oligodendrocyte plasma membranes, Cx30 and Cx43 were fo und only in astrocyte membranes, and Cx36 was only in neurons. Oligodendroc ytes shared intercellular gap junctions only with astrocytes, with each oli godendrocyte isolated from other oligodendrocytes except via astrocyte inte rmediaries. Finally, neurons shared gap junctions only with other neurons a nd not with glial cells. Thus, the different cell types of the CNS express different connexins, which define separate pathways for neuronal versus gli al gap junctional communication.