Chemistry of Gap Junctions

Gap junctions [also called nexus (15) or maculae communicantes (102)] repre­ sent transcellular channels that permit the exchange of small molecules and ions between neighboring cells (28, 33, 74, 75, 82, 86, 89, 103). They differ from other membrane channels in a number of respects: they provide a pathway between cells rather than across one cell membrane; they are nonspecific; and they allow for passive diffusion. Gap junctions link cells to their neighbors in almost every organ of the body (31) and are essentially ubiquitous in the animal kingdom; they can be recognized in many systems by their very characteristic morphology. In thin sections they are seen as paired parallel plasma mem­ branes of unusually smooth outline, separated from each other by a narrow space of constant width (94, 97), the gap. In freeze-cleaved (39, 55)[or negatively stained (35)] specimens, patches of closely packed membrane particles (the connexons) (41) in one membrane are in register with similar structures in the membrane of the apposed cell (10). Each connexon presum­ ably consists of protein subunits arranged so as to form a channel (9, 101, 112). From a physiological standpoint they allow for electrical coupling or exchange of molecules up to 800-1200 daltons (28-30, 86, 103). Permeability of the junction can usually be modulated by changes in pH (105, 111), pC02 (110), pCa (83, 98, 99), or membrane potential (46, 104). It is the purpose of this paper to review what is known about the chemistry of these proteins and to analyze our understanding of the relationship between their structure and the overall organization and physiology of gap junctions [recent reviews are found