Dissertation Gap Junctions

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Title: Navigating the Challenges of Dissertation Writing on Gap Junctions

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These hydrated gels resist compression (useful for joints). Two pairs of connexons (hexamers of connexins; Cx) form a pore enabling diffusion for ions and small molecules. Significant progress has been made in the technique of genetically encoded voltage indicator ( Kang et al., 2019 ). However, this state-of-the-art technique is still below the threshold to detect the subtle variation of voltages in an astrocyte syncytium, and therefore, future optimization of this technique is crucial to recruit advanced imaging techniques to study the physiology and pathology of astrocyte syncytial networks. Incubation with SR101 of slices from epileptic mice 9 mpi resulted in astrocytic labeling in the contralateral CA1 region. Both human tissue studies and animal models of epilepsy have shown considerable changes in connexin expression after seizure activity. Block 5 Erik Kessler, Michael O’Brien, Bryan Richman Structure:. Meshwork of fine fibers within the cell Made up of three types of fibers Microfilaments, Intermediate Filaments, and Microtubules Gives the cell some structural support. Increasing evidence for the role of GJs in seizure initiation, epileptogenesis, and tissue synchronization has been presented in both human tissue studies and experimental models of epilepsy. Here, we will limit our discussion to this advanced paired recording mode and its application to analyze the functional connectivity of neighboring astrocytes. Identify the four major tissue types and describe their functions. In a subset of patients with tumors associated with acute seizures, even higher levels of Cx43 mRNA were observed. Tight Junctions. Occur when the membranes of two cells move close to each other in order to prevent molecules from passing between cells. Afterward, results can be gathered in a radar diagram to denote the degree of anisotropy and orientation of networks (C 2 ). Over time, the V M reaches a stationary level of -73 mV. In addition, uncoupling was prevented in Toll-like receptor 4 knockout mice. First, differing from paired recordings, V M,SS is measured from single electrode recordings. Both human tissue studies and animal models of epilepsy have shown considerable changes in connexin expression after seizure activity. Since the patch-clamp system is able for simultaneous current injection and membrane potential recording, now only two electrodes are used for paired recording. Several studies have demonstrated a role for GJ coupling in seizure activity, although these findings have been debated. For the interpretation of ion diffusion within the gap junction network, it is beneficial to analyze the spread of ions that is less effected by signaling cascades. Tissue composition Outline How are cells organized into tissues? I. Recently, ultrastructural details of astrocyte-astrocyte contacts have been revealed that explain how such a low inter-astrocytic resistance could be biophysically achieved ( Kiyoshi et al., 2020 ). ADHESION JUNCTION: Cytoskeletal fibers join between cells; flexible; tissues subject to mechanical stress. Learning Outcomes 4-1 Identify the four major types of tissues in the body and describe their roles. 4-2 Discuss the types and functions of epithelial tissue. This is important in generating a clear visual signal because the primary reaction, phototransduction, is a dirty process. Gap junctions. Gap junction coupling in the ovarian follicle. Subsequently, LY labeling can be combined with immunohistochemistry to determine the identity of coupled cells ( Binmoller and Muller, 1992; Konietzko and Muller, 1994 ). Tracers are usually loaded for several minutes into a single cell via the backfill of the patch pipette. Discuss the types and functions of epithelial tissues. S is significantly weaker in Bergmann glia networks than those established by velate astrocytes at the granular layer. In the present review we discuss mutations in ?Cx genes encoding Cx26, Cx30, Cx30.3 and Cx31 which lead to skin disease and deafness.

Group of similar cells common embryonic origin common function Histology study of tissues

Pathologist looks for tissue changes that indicate disease. 4 Basic Tissues (1). These are connections that allow for the direct passage of molecules between two cells. Thus, the V M,SS serves as a dynamic readout of the strength of syncytial coupling. These half channels join together, bridge the extracellular space in the process, and form the entire channel that spans both cell membranes. To address the electrical role of gap junctional coupling for astrocyte syncytium, a single electrode method was developed in 2016 with details described in the following “Astrocyte Syncytial Isopotentiality” section Although there was a decline in the mean levels of Cx43 mRNA expressed predominantly in astrocytes in the epileptic tissue, there was no significant change in the corresponding protein levels. Altogether, these findings support the role of electric coupling through GJs in VFOs and seizure synchronization. The authors point out that their findings do not rule out the possibility of a change in the dynamic state (open vs closed) of the GJs playing a role in epileptogenicity. Lee et al. used fluorescence recovery after photobleaching (FRAP) to quantify GJ coupling in tissue from patients who underwent temporal lobectomies for intractable epilepsy. Significance of cell-adh es ion: Formation of multiple layers of cells. Muscle tissue 4. Nervous tissue. Epithelial Tissue. Tissue composition Outline How are cells organized into tissues? I. Shortly thereafter, three independent research groups proved that chemical synaptic transmission was not necessary for the synchronization of neuronal activity in the CA1 region of the hippocampus. Specifically, primary astrocytes were derived ex vivo from the hippocampus, hyperexcitable parahippocampus, and the “normal” cortex Similarly, tetanus toxin blocks the release of inhibitory neurotransmitters across the synaptic cleft, thereby causing generalized muscular spasms. Finally, the kindling model of epilepsy involving repeated electrical stimulations is used to study the effects of repeated seizures on the brain. You can download the paper by clicking the button above. Simultaneously, tracers diffuse within the gap junction network. Therefore, the controls used in these studies should be taken into account when considering human tissue data. Discuss the types and functions of epithelial tissues. In the following section, we will first discuss the rationale, application, advantage, and limitation of the commonly used paired recording model and the newly developed syncytial isopotentiality measurement. Panels (A) and (B) modified from Zhong et al. (2016), and Panels (C) and (D) modified from Ma et al. (2016). This is important in generating a clear visual signal because the primary reaction, phototransduction, is a dirty process. These approaches are capable to reveal cellular heterogeneity causing electrical isolation of functional circuits, reduced iontransfer between different cell types, and anisotropy of tracer coupling. The efficiency of the junction is increased because each strand acts independently. Cell Junctions. -Intercellular bridges located between the cells of animals -2 major types. The most convenient approach is to measure the extent of tracer spreading in two directions orthogonal to each other (“YX ratio”). Both human tissue studies and animal models of epilepsy have shown considerable changes in connexin expression after seizure activity. Protein domain structure Dystrophin glycoprotein complex Contraction unit Cytoskeletal linkages at sarcolemma Muscle proteins and disease Creatine kinase and CKI In situ staining and Western blots. These approaches include paired recordings, determination of syncytial isopotentiality, tracer coupling followed by analysis of network topography, and wide field imaging of ion sensitive dyes. Electrophysiological studies have implicated GJs in the generation of very fast oscillations that precede seizures. Biophysically, gap junctional ionic movement occurs during the equalization of the potential differences in a syncytium, therefore a strong syncytial isopotentiality means a less ionic movement inside a syncytium.

In contrast, Maier et al. (2002) showed that hippocampal slices from mice lacking Cx36 had less frequent sharp waves and ripple oscillations. No changes in Cx37, connexin 40 (Cx40), or Cx47 mRNA were observed after KA treatment in rats. To unravel these particular differences suitable approaches are necessary. Here, the gap junctions insure efficient propagation of contractile signals so that the cardiac muscle can contract in synchrony. In addition, mefloquine, a specific Cx36 blocker, did not alter the seizure-like activity in the wild-type slices, indicating that the reduction in amplitude seen in the knockout slices was likely due to preexisting compensatory changes rather than due to the lack of the interneuron GJs. By extension, the gap junction coupled astrocytes should then be able to balance their membrane potentials to comparable levels so that a syncytial isopotentiality could be achieved. Thus, despite a striking difference in syncytial anatomy, the syncytial isopotentiality occurs to syncytial networks established by both subtypes of astrocytes ( Kiyoshi et al., 2018 ). Over time, the V M reaches a stationary level of -73 mV. Gap junctions are integral membrane proteins that connect the cytosol of neighboring cells. Introduction. Cell adhesion to polymer surfaces has obvious implications in the field of tissue engineering. As a result, many studies use tumor specimens as controls for epileptic tissue (and vice versa). These are connections that allow for the direct passage of molecules between two cells. Reading Cooper: Chapter 14 Topics The Extracellular Matrix Composition Cell-Matrix Interactions Cell-Cell Interactions. These approaches are capable to reveal cellular heterogeneity causing electrical isolation of functional circuits, reduced ion-transfer between different cell types, and anisotropy of tracer coupling. American colonists in Texas had to adapt to a different culture and government in Mexican Texas. Thus, independent of Cx isoforms, transjunctional voltage measurements stand out as an universal readout of gap junctional coupling ( Veenstra et al., 1995; Veenstra, 1996 ). Though astrocytes throughout the brain share similar properties, they exhibit a considerable amount of region-dependent heterogeneity. Learning Outcomes 4-1 Identify the four major types of tissues in the body and describe their roles. 4-2 Discuss the types and functions of epithelial tissue. Connexons in turn are hexamers that are formed by connexins (Cx; Figure 1A ). Both KA, a neuroexcitatory amino acid, and pilocarpine, a muscarinic receptor agonist, are commonly used to induce a model of temporal lobe epilepsy (TLE) in rodents. Incubation with SR101 of slices from epileptic mice 9 mpi resulted in astrocytic labeling in the contralateral CA1 region. Knockout and GJ inhibitors studies have demonstrated potential anticonvulsant effects, although these results are mixed and suffer from lack of specificity of many of the currently available GJ inhibitors. They found that Cx30 is the dominant astrocytic connexin in the thalamus and functional channels formed by Cx30 and Cx32 predominantly mediate astrocyte to oligodendrocyte coupling in the thalamus. For example, Kettenmann and Ransom used it to record cultured astrocytes and oligodendrocytes, confirming that gap junctions were indeed the molecular identities for the functional coupling of these glial subtypes ( Kettenmann and Ransom, 1988; Ransom and Kettenmann, 1990 ). A summary of the various cell junctions found in a vertebrate. Mutations in Cx genes are linked to a range of human disorders. Increasing evidence for the role of GJs in seizure initiation, epileptogenesis, and tissue synchronization has been presented in both human tissue studies and experimental models of epilepsy. Anchoring junctions: attach cells (and their cytoskeleton) to other cells or extracellular matrix (providing mechanical support) 3. A significant disadvantage to human tissue studies is the lack of appropriate controls. From top to bottom, there are tight junctions (purple), adherens junctions with f-actin (blue), desmosomes (orange) connected to intermediate filaments, and gap junctions (blue).

Introduction. Tissue: Collection of specialized cells that perform limited number of functions

Histology: The study of tissues What are the four tissues of the body. Xylem - Chief conducting tissue for water and minerals that are absorbed by the roots. What are: atoms nucleus p rotons neutrons electrons energy levels a tomic number mass number molecule c ompound cation anion. Panels (A) and (B) modified from Zhong et al. (2016), and Panels (C) and (D) modified from Ma et al. (2016). Gap junctions. Gap junction coupling in the ovarian follicle. Findings implicating GJs in epilepsy as well as differences in the roles of neuronal versus glial GJs in tissue excitability are considered in this chapter. Gap junctions Regulation of connectivity When might a cell want to alter its connections to other cells. Something that is made by virtually all multi-cellular organisms. Elaborate covering outside animal cell membranes, occupying the space between cells. Metazoan cells form organs with specialized tissues:. - Epithelial. Cells. - Muscle. Cx30 mRNA was upregulated in the hypothalamus and in the medial amygdaloid nuclei by 6 hours. Both human tissue studies and animal models of epilepsy have shown considerable changes in connexin expression after seizure activity. Group of similar cells common embryonic origin common function Histology study of tissues Pathologist looks for tissue changes that indicate disease. 4 Basic Tissues (1). They found that Cx30 is the dominant astrocytic connexin in the thalamus and functional channels formed by Cx30 and Cx32 predominantly mediate astrocyte to oligodendrocyte coupling in the thalamus. Increasing evidence for the role of GJs in seizure initiation, epileptogenesis, and tissue synchronization has been presented in both human tissue studies and experimental models of epilepsy. A second disadvantage of human tissue studies is that they are often a representation of the end-point of a disease. No changes in Cx37, connexin 40 (Cx40), or Cx47 mRNA were observed after KA treatment in rats. Consequently, rather low CC values in the range from 1.6% to 5.1% were reported from hippocampal astrocytes in situ ( Meme et al., 2009; Xu et al., 2010 ). Cells (mesenchymal origin) - fibroblasts - smooth muscle cells - chondroblasts - osteoblasts and epitelial cells. Graham Cromar and Dr. John Parkinson Program in Molecular Structure and Function Hospital for Sick Children Toronto, ON, CANADA. More details about the biophysical principles and assumptions used to build up this computational model are available in this publication ( Kiyoshi et al., 2018 ). In addition, this model can be used for analysis of the dynamic change of coupling strength, for instance, during neuronal activation ( Kiyoshi et al., 2018 ). In a subset of patients with tumors associated with acute seizures, even higher levels of Cx43 mRNA were observed. Findings implicating GJs in epilepsy as well as differences in the roles of neuronal versus glial GJs in tissue excitability are considered in this chapter. Describe the relationship between form and function for each tissue type. For instance, when heart cells need to beat in unison, gap junctions allow for the transmission of electrical signals between the cells. There are also hemidesmosomes (orange) on the basal surface attached to the basement membrane. Taken together, these data suggest preseizure ripples are generated by electrical coupling of neurons and GJs are involved in the synchronization of VFOs. Interestingly, no changes in Cx43 mRNA levels were found in epileptic tissue compared to control. The efficiency of the junction is increased because each strand acts independently. The retina is an excellent example with numerous gap junctions between neurons. Learning Outcomes 4-1 Identify the four major types of tissues in the body and describe their roles. 4-2 Discuss the types and functions of epithelial tissue.

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