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Freeze Fracture in Lung Research
Published in Joan Gil, 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).
Ultrastructure of The Myometrium and The role of Gap Junctions in Myometrial Function
Published in Gabor Huszar, The Physiology and Biochemistry of the Uterus in Pregnancy and Labor, 2020
Arie Verhoeff, Robert E. Garfield
Gap junctions are present between most types of cells at least during some stage of the cell cycle, except between cells which are not part of an organized tissue (i.e., blood cells). Though present throughout the animal kingdom, the number of gap junctions varies considerably depending on the tissue type.40-46 Changes in the number, size, and distribution of gap junctions have been described as part of many developmental cell processes including growth and maturation.38-42,44,46,53-55 Gap junctions appear to be dynamic structures in most cell systems. The formation of gap junctions has been studied primarily in vitro where cells are separated and allowed to reaggregate and form communicating junctions.43,49,54 In cell systems where gap junctions are believed to be dynamic structures, gap junction degradation is supposed to occur by either dispersal of gap junction particles within the plasma membrane or internalization of the entire gap junction within one of the cells by endocytosis and degradation by lyso-somes.40,43 The latter mechanism has been suggested because internalized gap junctions (annular) have been observed in many cell types.43
Role of Cell-to-Cell Coupling in Control of Myometrial Contractility and Labor
Published in Robert E. Garfield, Thomas N. Tabb, Control of Uterine Contractility, 2019
Gap junctions are intercellular channels that link cells to their neighbors and allow the passage of inorganic ions and small molecules.56,72,75,80,89 They have been found between cells in every tissue and organ examined and are essentially ubiquitous in the animal kingdom. In electron micrographs of thin sections, they appear in regions of close opposition between cells as zones of paired, parallel membranes of unusually smooth outline separated by a narrow space of constant width—the gap—about 2 to 3 μ M (Figures 2 and 3). In freeze fracture replicas vertebrate gap junctions appear as arrays of 8 to 9.5-μ M membrane proteins organized into circular or oval plaques (Figures 4 and 5).
Investigational drugs in phase II clinical trials for acute coronary syndromes
Published in Expert Opinion on Investigational Drugs, 2020
Amit Rout, Ajaypaul Sukhi, Rahul Chaudhary, Kevin P Bliden, Udaya S Tantry, Paul A Gurbel
Connexins are proteins that are structurally assembled to form the gap junctions. Connexin 43 is the isoform found in cardiomyocytes and vascular endothelium. It plays an important role in electrochemical signaling and ischemia-reperfusion injury. Connexin 43 found in mitochondria of cardiomyocytes is involved in the formation of reactive oxygen species and plays a role in ischemic preconditioning [102]. Danegaptide (Zealand pharma, Copenhagen, Denmark) is a dipeptide and, a second-generation oral gap junction modifier, which is similar to its parent drug rotigaptide and has antiarrhythmic properties [103]. This drug had shown cardio-protective effects in terms of reducing infarct size in animal models [104]. In a phase II trial (NCT01977755), STEMI patients were randomized to either two different doses of danegaptide or placebo, which was administered 10 minutes prior to PCI and lasted for 6 hours. The primary outcome of myocardial salvage evaluated by cardiac MRI at 3 months was similar between danegaptide and placebo (p = 0.88). The secondary outcome of infarct size and left ventricular ejection fraction was also similar between the two groups [105]. So far, no further studies are planned for danegaptide.
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].
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)