Connexin and Pannexin Based Channels in the Nervous System: Gap Junctions and More

The coordination of cell functions is a challenge for all organ systems of the body. This is achieved in part through a variety of exocrine and endocrine mechanisms that involve the complex release of signals from cells, their detection by receptors in other cells, and the ultimate generation of an intracellular response in the target cell. However, there is also an ancient mechanism that evolved with the earliest of multicellular organisms whereby signals, nutrients and other metabolites under about 1,000 in MW are exchanged directly between adjacent cells without dilution through the extracellular environment. This occurs through structures called gap junctions. The nervous system is no exception to this. Gap junctions are present at homocellular and heterocellular contacts between most cells in the CNS and PNS, including astrocytes, oligodendrocytes, microglia, endothelial and ependymal cells and some neurons. Between neurons, gap junctions have a unique role in that they form electrical synapses, which contrast with, and complement, the role of the more extensively studied chemical synapses that predominate in the nervous systems of most animals above the Coelenterates. This chapter discusses the functional significance of electrical synapses in the nervous system, as well as other roles of gap junctions associated with the intercellular transport of metabolites and signals between not only neurons, but many cell types within the CNS. The significance of hemichannels, which form away from sites of cell-cell contact and allow exchanges of similar repertoire of molecules with the extracellular environment, is also considered, along with roles of the gap junction as a nexus for signaling and an adhesive structure between cells of the nervous system. Misregulated or abnormal hemichannels and/or gap junction channels contribute to both acquired and genetic pathologies, and their roles in specific disease states, including knockout phenotypes, are discussed.