The Ultrastructure And Pathobiology Of Urinary Bladder Cancer
George T. Bryan, Samuel M. Cohen in The Pathology of Bladder Cancer, 2017
Gap junctions mediate a form of intercellular communication which involves the direct exchange of ions and molecules from cell to cell without leakage into the intercellular space.125-127 This form of cell-to-cell transfer of substances can be measured as a function of transmembrane electrical resistance or as a function of the sufficiency of time for metabolic exchange from one cell to another.128 In mammalian cells, it has been shown that the hydrophilic channels of gap junctions accommodate probe molecules with molecular weights under 900 daltons.129 Falling within this size range is a rather long list of substances that includes potential morphogens and inhibitors. By providing conduits for the transfer of informational molecules from cell to cell, gap junctions may participate in the regulation of diverse activities including tissue metabolism, growth, and differentiation.125,130,131
Role of Cell-to-Cell Coupling in Control of Myometrial Contractility and Labor
Robert E. Garfield, Thomas N. Tabb in Control of Uterine Contractility, 2019
The potential for rapid closure of gap junctions serves several functions: to isolate healthy cells from damaged neighbors and thereby prevent the loss of small cytoplasmic components, and also to allow rapid adjustment of coupling levels to changing circumstances. Experimentally, cell coupling can be rapidly and reversibly blocked or enhanced with modulation of permeability occurring within seconds or minutes, according to the following, apparently independent mechanisms: (i) intracellular Ca2+ and intracellular pH, (ii) intracellular cAMP and phosphorylation, and (iii) transjunctional voltage.80,89 Many pharmacological agents that modulate either gap junction number or permeability can thereby dramatically alter tissue function.89
Ultrastructure of The Myometrium and The role of Gap Junctions in Myometrial Function
Gabor Huszar in The Physiology and Biochemistry of the Uterus in Pregnancy and Labor, 2020
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
Biological therapies targeting arrhythmias: are cells and genes the answer?
Published in Expert Opinion on Biological Therapy, 2018
Debbie Falconer, Nikolaos Papageorgiou, Emmanuel Androulakis, Yasmin Alfallouji, Wei Yao Lim, Rui Providencia, Dimitris Tousoulis
The aim of cell therapies is to restore normal function of the conduction system in the heart by transplantation of appropriate cell populations [28]. Two strategies have been explored with regard to formation of cell-based biological therapy for use in arrhythmogenesis. The first involves the injection of unexcitable cells expressing inward current that depolarizes neighboring cells to their action potential threshold. This method requires at least two cells to create a pacing unit. The second strategy involves the injection of excitable cells with the ability to generate spontaneous action potentials. In this method, the delivered cells are the biological pacemakers. In both strategies, the assumption is that coupling will occur through gap junction formation between donor cells and between donor and target cells. Gap junctions are required for the initiation of intercellular current flow allowing the delivered cells to integrate electromechanically into the cardiac environment [29].
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].
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.
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