The structure and permeability of isolated hepatocyte gap junctions

Abstract

The ultrastructure of the gap junction may be visualized in both in situ and isolated preparations by using a variety of electron microscope techniques. The junction is composed of a lattice of subunits, called connexons, which show variable degrees of packing into a hexagonal lattice depending on a variety of poorly understood conditions. In general, it appears that more uncoupled and "dead" the junction, the more regular and condensed the hexagonal lattice becomes. It is not yet known whether these are "postmortem" changes or physiologically active and reversible changes involved in regulation of junctional permeability. Using a variety of techniques, it can be seen that the connexon extends completely across the junctional membranes, from the cytoplasmic surface of one cell to the cytoplasmic surface of the other, spanning the 2-nm "gap" between the apposed junctional membranes. Thus it is possible to implicate the connexon as a permeability channel from cytoplasm to cytoplasm, although the hydrophilic pore through the center of the connexon has not yet been demonstrated to span the full junction thickness. X-ray diffraction experiments support these conclusions, and the excellent correlation between the electron microscope and X-ray diffraction data lends great confidence to the interpretations of gap junction structure presented thus far. These data are summarized in the drawing in Figure 17. This is a scale drawing of two connexons, each of which is imagined to be composed of a dimer of hexamers. It must be emphasized that as yet there is no direct evidence for a sixfold symmetry within the connexon. Of special interest now are the types of protein-protein interactions that hold the two halves of the connexon together across the 2-nm gap and the lateral interactions between the connexons at the level of the lipid bilayers.