13.14: Gap Junctions

Unlike the other types of cell-cell adhesion, the gap junction (sometimes called a nexus) connects not only the outside of two cells, it connects their cytoplasm as well. Each cell has a connexon (aka hemichannel) made of six connexin proteins. The connexins may be all of the same type, or combinations of different ones, of which there are 20 known in humans and mice. The connexon interacts with a connexon on an adjacent cell to connect the cytoplasm of both cells in a gap junction.

Figure \(\PageIndex{18}\). Gap Junctions

The gap junction pore size varies depending on the type of connexins, but generally, the molecules under 1 kDa are able to pass through while larger ones can not. Therefore, cells connected by gap junctions are electrically connected (ions can freely pass), they can share cellular energy (ATP), and second messenger signaling molecules like Ca²⁺ or IP₃, but not most proteins or nucleic acids. The pores are not always open, but are controlled by phosphorylation of several serines in the intracellular domains of each connexin.

Although they have now been found in most metazoan tissue types, they are particularly important in heart muscle. Here, the gap junctions insure efficient propagation of contractile signals so that the cardiac muscle can contract in synchrony. It is also important in cardiac development: gene knockout of connexin43, the primary heart connexin, leads to delayed looping of the ascending limb of the embryonic heart tube, which means malformations especially in the right ventricle, tricuspid valve, and subpulmonary outflow tract.

Figure \(\PageIndex{19}\). An overview of cellular adhesions. From top to bottom, there are tight junctions (purple), adherens junctions with f-actin (blue), desmosomes (orange) connected to intermediate filaments, and gap junctions (blue). There are also hemidesmosomes (orange) on the basal surface attached to the basement membrane

When most people, including most biologists, think about neuronal connections and synapses, they think of chemical synapses in which one cell signals to another by release of neurotransmitters. However, it is now well established that in the CNS, electrical synapses through gap junctions are a significant part of the repertoire of neural communication. The retina is an excellent example with numerous gap junctions between neurons. In fact, light-activated neurotransmitters can activate protein kinase pathways that phosphorylate connexins, thus altering conductance through the gap junctions. A striking example is the gap junction-based electrical coupling of cone photoreceptor neurons. They are coupled near the base of the cells, so that excitation of one drives excitation of several others. This is important in generating a clear visual signal because the primary reaction, phototransduction, is a dirty process. Due to the simple presence of random photons bouncing about, the signal to noise ratio of light-induced excitation is very low. However, because electrical coupling sums up the signal of near neighbors but not the background noise, the signal output from these neurons has an improvement in signal to noise ratio of ~77%! This topic is reviewed in Bloomfield and Volgyi, Nature Reviews (Neuroscience), 10:495-506, 2009.