Ion Channels in Immune Cells
Shyam S. Bansal in Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Gap junctions are formed when two opposing hexameric connexons, also called connexin hemichannels, that are present on respective cells dock to each other. Hemichannels can be homomeric (composed of the same connexins) or heteromeric (composed of different connexins)162. Gap junctions formed of two homomeric or two heteromeric hemichannels with the same connexin composition are called homotypic gap junctions. Heterotypic gap junctions are formed by two hemichannels, each with a different composition of connexins163. Cardiac muscle predominantly expresses connexin 40 (Cx40), connexin 43 (Cx43), connexin 45 (Cx45), and connexin 37 (Cx37) in humans and rodents159,164. These connexins are differentially expressed in various regions of the heart. For instance, Cx40 is expressed in atrial cardiomyocytes, and Cx43 is mainly expressed between the atrial and ventricular conduction system161.
Synapses
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
Electrical synapses, as commonly understood, have a direct connection between the cytoplasms of two cells by means of gap junctions consisting of at least several hundreds of channels (Figure 6.18). In vertebrates, these channels are made up of isoforms of the protein connexin having a molecular mass in the range of 26–57 kD, where a protein isoform is one of the different forms of the same protein. Six connexin molecules, not necessarily identical, form a hexameric hemichannel, or connexon, about 5–7.5 nm long and with an external diameter of about 7 nm. A connexon spans across the cell membrane and extends for 1–1.5 nm into the extracellular space. Each connexon has six protrusions, one from each of the connexin molecules, that fit into the depressions between the protrusions of the other connexon of the channel. A channel having a pore of 1.2–2 nm diameter is thus formed, with tight interlocking in the extracellular gap of 2–3.5 nm separating the membranes of the two cells. The tight interlocking is necessary to prevent leakage of ions between the channel and the extracellular space. The two connexons are held together noncovalently by hydrogen, hydrophobic, and ionic bonds between the extracellular loops of the connexin molecules.
Freeze Fracture in Lung Research
Joan Gil in Models of Lung Disease, 2020
Gap junctions represent transcellular channels that permit the exchange of small molecules and ions between adjacent cells (Gilula et al., 1972; Potter et al., 1966). While they are ubiquitous, not all epithelial and endothelial cells are linked by them at any given time. By freeze fracture, gap junctions are shown to form patches of closely packed membrane particles (connexons) that are in register with similar particles in the membrane of the adjacent cell (Fig. 1). Each connexon consists of protein subunits, arranged to form a central channel that allows electrical coupling and the exchange of molecules of up to 800-1,200 daltons. Permeability of the gap junction can be modulated by changes in pH, pCo2, Ca2+, or membrane potential. Studies of their structural organization within the membrane, their regulation, and biochemical composition are underway (for a review see Revel et al., 1985).
Genetic investigation of ocular developmental genes in 52 patients with anophthalmia/microphthalmia
Published in Ophthalmic Genetics, 2018
Nair Gopinathan Vidya, Sankaranarayanan Rajkumar, Abhay R. Vasavada
Gap junctions which are formed by two hemichannels (connexons) are involved in cell to cell transfer of ions, peptides, ATP, and other nutrients. Gap junctions are composed of four conserved transmembrane domains, two extracellular loop domains, one intracellular loop domain, and cytoplasmic amino and carboxy-terminal domains. (28) In the human lens, there are three types of gap junctions: 1) GJA1 which is present in lens epithelial cells, 2) GJA3 which is predominantly expressed in the lens fiber cells, and 3) GJA8 that is expressed in lens epithelial and fiber cells. (29–31) Mutations in both GJA3 and GJA8 have been associated with autosomal dominant congenital cataract and age-related cataract (28,32–42) while GJA8 mutation is also associated with microphthalmia, microcornea, and sclerocornea. (34,43,44)
Gingival epithelial barrier: regulation by beneficial and harmful microbes
Published in Tissue Barriers, 2019
Naoki Takahashi, Benso Sulijaya, Miki Yamada-Hara, Takahiro Tsuzuno, Koichi Tabeta, Kazuhisa Yamazaki
A primarily structural bond between epithelial cells is created by junctional molecules, including tight junctions, adherens junctions, and gap junctions8,26 (Figure 1). Tight junctions are responsible for paracellular transport of ions, water, and solutes due to their semipermeable structure.28 Several proteins are found in the tight junctions, such as occludin,29 claudins,30 and zonula occludens (ZO) protein ZO-1, ZO-2, and ZO-3.30–32 Occludin has been detected in the gingival epithelium’s surface layer, whereas claudin-1 was found in the uppermost layer.26 Claudins have barrier properties, which directly regulate gate function at paracellular tight junction channels.30 Adherens junctions play a vital role in controlling the junctional complex activity.8 Adherens junctions are cell-to-cell adhesion sites where the actin-based cytoskeleton and cytoplasmic components are constructed, also known as the classic cadherins function.33 The intercellular communication in gap junctions is involved in homeostasis, regeneration, and developmental processes.34 Furthermore, gap junctions regulate the reciprocal exchange of metabolites and ions of molecular weight ≤1 kDa, such as cyclic adenosine monophosphate and Ca,35+ between adjacent cells. The form of this junction is a head-to-head docking of hexameric structures called connexons, and membrane proteins called connexins.36
Progress of co-culture systems in cartilage regeneration
Published in Expert Opinion on Biological Therapy, 2018
Jianyu Zou, Bo Bai, Yongchang Yao
Many researchers devote themselves to investigating the underlying mechanisms in direct co-culture systems. Some suppose that the direct cell-cell contact may result in the cell fusion of the different types of cells to form heterokaryons [36,86]. Some believe that direct physical contact facilitates the close intercellular communication and signal transmission among the co-cultured heterologous cells via autocrine and paracrine ways [34,87]. Some note that connexons, expressed by chondrocytes, form gap junctions and enhance cell signal exchange and further improve tissue formation [83,88]. Recently, a comprehensive study was carried out to determine the mechanisms behind co-culture systems [25]. This study employed a cytosolic dye transfer test and connexin 43 (a gap junction protein) staining to confirm that the communication between human articular chondrocytes and human bone marrow-derived MSCs in the direct co-culture system is through gap junctions. Gap junctions are of great importance in cell–cell connections by the exchange of nutrients and the transduction of molecular signals [89].
Related Knowledge Centers
- Cell Signaling
- Cytoplasm
- Extracellular Space
- Gap Junction
- Membrane Channel
- Oligomer
- Connexin
- Endoplasmic Reticulum
- Cell
- Heteromer