Gap junctions are clusters of cell-cell channels. These cross the cell membranes of two neighboring cells and provide a connection between the cytoplasm.
What is a gap junction?
Gap junctions are so-called connexons (protein complexes) that connect the plasma membrane of two cells. The membranes are fixed, but a gap is still visible under the electron microscope. The channels of a gap junction consist of two half-channels (connexon). A connexon is made up of protein complexes that come together in the shape of a hexagon. A pore remains free in the middle. A channel is formed from two such protein complexes. With the help of gap junctions, the exchange of signals between cells is possible. Molecules or ions can be transferred by diffusion, and these can be metabolites, secondary messengers, or calcium ions.
Anatomy and structure
The term gap junction was coined by Morris Karnovsky and Jean-Paul Revel. They found that in the region of a gap junction, the distance between two neighboring membranes narrows. A gap junction consists of six connexins, which together form a so-called connexon. A connexon can be composed either of different connexins or of the same type of connexins. A connexin consists of a polypeptide chain formed by two extracellular loops, four transmembrane domains, and an N- and C-terminus, respectively. The length of the C-terminus determines the molecular weight. In humans, there are at least 20 connexin genes, and the designation of the different connexin isoforms is based on molecular weight. S
o example, connexin 43 has a weight of 43kDa. A gap junction is very often composed of several isoforms. The functional significance of this diversity is not fully understood; it is likely that the patency of the channels can be regulated differently as a result. A hemichannel is then connected to the hemichannel of a neighboring cell. This intercellular channel is either composed of different connexons or of two identical connexons. The diameter of the pore is 1.5 to 2nm, allowing ions or molecules to pass. A gap junction can be established within a few seconds when two cells come into contact. Connexons are arranged in a hexagonal pattern, with about 28,000 channels per square micrometer forming so-called plaques.
Function and tasks
Gap junctions are particularly widespread in the embryonic stage. In adults, they can be found in the retina, glial and epithelial cells, and cardiac muscle. Gap junctions perform the following functions:
- Establishing direct electrical communication between cells.
- Establishment of direct chemical communication via so-called second messengers.
- Molecular exchange between cells
- Preventing charges or molecules from being lost in the exchange process.
Gap junctions serve to transport nutrients in bones or the lens of the eye, for example. The nutrients are taken up by the marginal cells and then passed on to the neighboring cells via the gap junctions. In the pancreas and liver, they support secretion, while in the nervous system or heart muscle they transmit action potentials. Gap junctions can close pores extremely quickly. This occurs, for example, when a neighboring cell is damaged. The neighboring cell is subsequently disconnected, leaving the healthy cells undamaged. In the heart, in the retina or in neurons, gap junctions function as transmitter-free, voltage-gated synapses, also called “electrical synapses”. This allows action potentials to propagate very quickly and synchronously. The conductance here depends on the composition of the connexins.
Diseases
If changes occur in the construction of gap junctions, this can lead to various diseases. For example, in the so-called Charcot-Marie-Tooth syndrome, a blockage occurs between the periaxonal cytoplasm and Schwann cell, resulting in Schwann cell degeneration. Tumor cells lose their ability to communicate due to the production of oncogenes and tumor promoters. Gap junction channels close and incompatible connexins are formed, causing tumor cells to grow.Altered connexin expression also occurs in inflammatory processes. When cardiac gap junctions are altered, this leads to cardiac arrhythmias that can be life-threatening. Impairments in the function of gap junctions in the heart often have very different causes. In the so-called Chagas disease, an infection with Trypanosoma cruzii occurs, as a result of which the gap junction channels are only incorporated into the membrane to a reduced extent. In acute myocardial infarction, gap junctions close, decreasing action potential duration. In the postinfarction period, gap junctions are redistributed, and changes in the distribution of gap junctions also occur in chronic heart failure, in which case the gap junctional surface area in particular is reduced. Furthermore, a disturbance of the gap junction proteins can also lead to congenital deafness, congenital infertility or skin diseases. Furthermore, gap junction channels play an essential role in cataracts. The lens of the eye cannot supply itself with blood because blood vessels make the lens body opaque. As a result, the cells in the lens are dependent on neighboring cells, with the supply coming through the gap junction channels. If a breakdown in communication occurs, the cells die and cataracts form.