Introduction

-‘he big news is that gap junctions of different kinds are formed by a number of homologous proteins termed connexins, which are encoded by a gene family. Specific connexins are expressed in more than one tissue, and a single cell type may express more than oneconnexin. Differences between gap junctions can result from differences between the connexin or connexins forming them, as well as from differences between the cells expressing a given connexin. Specific antibodies and nucleotide probes for the connexins are allowing study of distribution, function, and differential regulation of their expression. Moreover, their conductance can now be studied at the singlechannel level. Finally, exogenous expression systems permit analysis in controlled environments and with specifically modified cDNAs and cRNAs. Classically, gap junctions are defined by thin section images in which membranes of apposed cells c, losely approach each other, but where a small gap of’-2 nm separates the membranes (Figure IA). Connexin-specific antibodies now permit recognition of putative gap junctions at the light microscopic level, which can then be confirmed by immunolabeling and electron microscopy (Figures IC and ID). Electron mi-(roscopy and image reconstruction of isolated junc-tions indicate that a single gap junction channel is a tlodecamer formed by six monomers in the memhrane of each of the two coupled cells. The channel connecting the cell cytoplasms lies at the center of the oligomer. The walls of the hemichannels or connexons in each membrane contact each other in the middle of the intercellular gap to complete the coupling pathway. In spite of much new structural information (Makowski, 1988; Unwin, 1989), the general structure of the junctions is still well depicted in the 1% year-old drawing of Casper and Goodenough (Figt; re IB; Makowski et al., 1977). The gap junction channel admits passage of small molecules, which may be positively or negatively charged or neutral and up to-1 kd in size. The minimal channel diameter is about 1.2 nm in vertebrates and somewhat larger in insects (Schwarzmann et al., 1981). Proteins and nucleic acids are excluded, whereas many second messengers and small molecules of intermediate metabolism are permeant; the junctions s; re dramatically less selective than nonjunctional (hannels in the surface membrane (Siez et al., 1989a).

Thus, for small molecules coupled cells are functionally syncytial. However, one should not infer that concentrations are uniform among coupled cells; uniformity of concentration will depend on differences among cells in rates of production and removal of the molecule in question, on the number and specific permeability of the junctional channels, and on distance. In excitable cells, including cardiac muscle, neurons, certain smooth muscles, and fi cells of pancreatic islets, gap junctions transmit electrical signals. In inexcitable cells, gap junctions may act simply to buffer concentrations of metabolites among cells, or they may transmit regulatory molecules. An attractive idea is that gap junction communication mediates induction and the establishment of developmental fields in embryos (Furshpan and Potter, 1968; Bennett et al., 1981).