Figure 19–24 Determining the size of a gap-junction channel. When fluorescent molecules of various sizes are injected into one of two cells coupled by gap junctions, molecules with a molecular weight (MW) of less than about 1000 daltons can pass into the other cell, but larger molecules cannot. thus, the coupled cells share their small molecules (such as inorganic ions, sugars, amino acids, nucleotides, vitamins, and the intracellular signaling molecules cyclic aMp and inositol trisphosphate) but not their macromolecules (proteins, nucleic acids, and polysaccharides).
1.5 nm in diameter (C) 1.4 nm
Gap junctions in different tissues can have different properties because they are formed from different combinations of connexins, creating channels that differ in permeability and regulation. Most cell types express more than one type of connexin, and two different connexin proteins can assemble into a heteromeric connexon, with its own distinct properties. Moreover, adjacent cells expressing different connexins can form intercellular channels in which the two aligned half-channels are different (see Figure 19–25B).
Like conventional ion channels (discussed in Chapter 11), individual gap-junction channels do not remain open all the time; instead, they flip between open and closed states. These changes are triggered by a variety of stimuli, including the voltage difference between the two connected cells, the membrane potential of each cell, and various chemical properties of the cytoplasm, including the pH and concentration of free Ca2+. Some subtypes of gap junctions can also be regulated by extracellular signals such as neurotransmitters. We are only just beginning to understand the physiological functions and structural basis of these various gating mechanisms.
Each gap-junctional plaque is a dynamic structure that can readily assemble, disassemble, or be remodeled, and it can contain a cluster of a few to many thousands of connexons (see Figure 19–23B). Studies with fluorescently labeled connexins in living cells show that new connexons are continually added around the periphery of an existing junctional plaque, while old connexons are removed from the middle of it and destroyed (Figure 19–26). This turnover is rapid: the connexin molecules have a half-life of only a few hours.
The mechanism of removal of old connexons from the middle of the plaque is not known, but the route of delivery of new connexons to its periphery seems clear: they are inserted into the plasma membrane by exocytosis, like other integral membrane proteins, and then diffuse in the plane of the membrane until they bump into the periphery of a connexon plaque and become trapped. This has a corollary: the plasma membrane away from the gap junction should contain connexons—hemichannels—that have not yet paired with their counterparts on another cell. It is thought that these unpaired hemichannels are normally held in a closed conformation, preventing the cell from losing its small molecules by