Gap junction definition
Gap junction (also known as communicating junctions) refers to the type of cellular junction that allows passage of ions and small molecules between the cytoplasm of adjacent cells. This exchange is done through formation of a protein channel in cell plasma membrane.
Cellular communication and cell junctions
Formation of functional tissues and organs depends on communication and adhesion between adjacent cells. After adhering, cells form different types of specialized joints: anchoring junctions allow maintenance of cell shape and, consequently, tissues shape; tight junctions are responsible for making a barrier of one (or several) layer(s) cells that prevents passage of water and some solutes; and finally, gap junctions make possible cell communication, facilitating the exchange of ions and some molecules between adjacent cells.
Gap junctions’ characteristics
Cells in a tissue/organ are in direct and constant contact due to presence of a specific type of cellular junction: the gap junctions. These cellular junctions are responsible for allowing passage of ions, small molecules and electrical signals between adjacent cells that form a tissue.
Gap junctions are composed of 12 connexin monomers, which is a 4-helical transmembrane protein, with a molecular weight of 30 to 42kD. Each cell has 6 connexin monomers arranged in a three-dimensional arrangement, forming a hexagonal transmembrane pore with a diameter of 20Å, filled with water – the connexon. The extracellular portion of a cell pore proteins (which is actually half the final channel) comes into contact with the extracellular portion of cell neighbour pore proteinsl, forming a continuous channel. At the site of gap junctions, cells are separated by a space of only 2 to 4nm.
Figure 1 – Illustrative schematic image of a gap junction. A) open channel; B) closed channel; C) connexon; D) connexin monomer; E) plasma membrane of two adjacent cells; F) intercellular space; G) space from 2 to 4nm; H) hydrophilic channel.
These cellular junctions are located and distributed throughout cell lateral wall and thus facilitate the movement of small molecules (such as ions, sugars, amino acids, vitamins, among others) and electrical signals between two cells. On the other hand, gap junctions are a barrier to the passage of macromolecules (such as proteins and nucleic acids) due to their large size. A very important molecule that moves through gap junctions is cyclic AMP, necessary for synthesis of DNA and RNA.
In plant cells, there is only one type of gap junction and it is called ‘plasmodesmata’. Although structurally different, plasmodesmata have functions very similar to gap junctions present in animal cells. In mammalian cells, most cells in tissues communicate through gap junctions, which allow the passage of molecules with a diameter of up to 1.2 nm. Exceptions to this rule are cardiac muscle cells and cells present in the blood. In insects, molecules with a diameter of up to 2nm can pass through these junctions. In humans, there are 14 different connexins, which reflects the various properties of gap junctions present in different tissues.
Gap junctions’ types
Electrical synapses
Electrical synapses are characterized by the existence of gap junctions between adjacent neurons. This feature makes possible the fairly rapid transmission of action potential, and the passage of ions between presynaptic neuron and postsynaptic neuron. This type of synapse is very important in some fish and insects, but uncommon in vertebrates.
However, electrical synapses occur not only in neurons, but also in other cell types, such as smooth muscle cells in the intestine and mammalian heart muscle cells. These cells are said to be electrically bound, which means that action potential starts in a cell and passes through gap junctions to neighbour cells. The existence of gap junctions in cardiac muscle cells causes the heart muscle to contract as a whole, leading the blood in one direction.
Other gap junctions
Gap junctions are also important in non-excitable tissues. They are important, for example: for ovarian follicles development; for fetus development and differentiation at the embryonic stage; and in liver upon the fall of glucose levels leading to glycogen cleavage and liver glucose release into the blood.
Gap junctions’ channels regulation
Channels forming gap junctions are not permanently open or closed. Instead, they transit from one state to another in seconds/minutes, being controlled by both intracellular and extracellular signals.
One of intracellular signals is cytosol concentration of calcium, which is highly controlled. Due to the large difference in calcium concentrations between extracellular medium (high concentration) and intracellular medium (low concentration), this ion is an important regulator of gap junctions’ channels opening and closing. Even small increases in cytosol calcium concentration lead to decreased permeability of gap junctions. The decrease in pH, membrane potential and hormone-induced phosphorylation are also intracellular signals that control opening and closing of these channels. Neurotransmitters act as an extracellular regulatory signals.
Gap junctions study
Gap junctions study can be done electrically or by microinjection of water-soluble fluorescent dyes, then using a fluorencence microscope for observation. Through this technique it is possible to determine the channel size by attaching dyes to molecules of different molecular weight and analyzing which ones pass freely to neighbour cells by the pore and which do not.
References:
Alberts B., Johnson A., Lewis J., Raff M., Keith R., Walter P. (2007). Molecular Biology of the Cell (5th edition). Garland Science, New York.
Berg J.M., Tymoczko J.L., Stryer L. (2002). Biochemistry (5th edition). W. H. Freeman, New York.
Cooper G.M. (2000). The Cell: A Molecular Approach (2th edition). Sinauer Associates, Sunderland (MA).
Lodish H., Berk A., Zipursky S.L., Matsudaira P., Baltimore D., Darnell J. (2000). Molecular Cell Biology (4th edition). W. H. Freeman, New York.
