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  • 1
    ISSN: 1540-8167
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: AV Nodal and Infra-Hisian Conduction in Cx40 Mice. Introduction: Previous electrophysiologic investigations have described AV conduction disturbances in connexin4(Cx40)-deficient mice. Because expression or(Cx40 occurs predominantly in the atria and His-Purkinje system of the mouse heart, the AV conduction disturbances were thought to be secondary to disruption in His-Pnrkinje function. However, the lack of a His-bundle electrogram recording in the mouse has limited further investigation of the importance of Cx40. Using a novel technique to record His-bundle recordings in Cx40-deficient mice, we define the physiologic importance of defciencies in Cx40.Methods and Results: Ten Cx40-/- mice and 11 Cx40+/+ controls underwent a blinded, in vivo, closed chest electrophysiology study at 9 to 12 weeks of age. In the Cx40+/+ mice, the PR interval was significantly longer compared with Cx40+/+ mice (44.6 ± 6.4 msec vs 36.0 ± 4.1 msec, P = 0.002). Not only the HV interval (14.0 ± 3.0 msec vs 10.4 ± 1.2 msec, P = 0.003) but also the AH interval (33.2 ± 4.8 msec vs 27.1 ± 3.7 msec, P = 0.006), AV Wenckebach cycle lengths, and AV nodal effective and functional refractory periods were prolonged in Cx40-/- compared with Cx40+/+ mice.Conclusion: Cx40-deficient mice exhibit significant delay not only in infra-Hisian conduction, as would be expected from the expression of Cx40 in the His-Purkinje system but also in the electrophysiologic parameters that reflect AV nodal conduction. Our data suggest a significant role of Cx40 in atrionodal conduction and/or in proximal His-bundle conduction,
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 283-310 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Intercellular channels present in gap junctions allow cells to share small molecules and thus coordinate a wide range of behaviors. Remarkably, although junctions provide similar functions in all multicellular organisms, vertebrates and invertebrates use unrelated gene families to encode these channels. The recent identification of the invertebrate innexin family opens up powerful genetic systems to studies of intercellular communication. At the same time, new information on the physiological roles of vertebrate connexins has emerged from genetic studies. Mutations in connexin genes underlie a variety of human diseases, including deafness, demyelinating neuropathies, and lens cataracts. In addition, gene targeting of connexins in mice has provided new insights into connexin function and the significance of connexin diversity.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Considerable evidence indicates a critical role for dopamine in the reinforcing effects of cocaine. Because dopamine has been shown to be a critical modulator of gap junction communication in both eye and brain, we sought to examine whether extended intravenous cocaine self-administration would affect the expression of gap junction channel-forming proteins (connexins). Using ELISA, Western analysis, immunohistochemistry, semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and non-radioactive in situ hybridization, we demonstrate that withdrawal from chronic cocaine self-administration causes lasting changes in connexin32 (Cx32) expression in the nucleus accumbens and hippocampus at 2, 7 and 21 days after the last cocaine injection. A sustained decrease in Cx32 protein and mRNA levels is noted in areas that have been implicated in cocaine craving (i.e. nucleus accumbens and subfields of the hippocampal formation). A progressive increase in gap junction protein and mRNA expression is noted in areas that become hyperexcitable after chronic cocaine exposure (i.e. CA1 hippocampal neurons). We speculate that gap junction communication may be critically involved in reinforcement processes and neuroadaptive changes produced by drugs of abuse.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 23 (1996), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The physiological significance of communication through gap junction channels has been difficult to assess because channel activity cannot be experimentally modulated in a specific manner. To address this problem we have constructed chimeric connexins that function as dominant-negative inhibitors of intercellular channel activity.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillan Magazines Ltd.
    Nature 394 (1998), S. 630-631 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Genetic deafness is one of the most prevalent inherited sensory disorders, affecting about 1 in 2,000 children. Mutations in the connexin 26 gene have been associated with autosomal recessive non-syndromic deafness (DFNB1). The connexin 26 gene is a member of the connexin family of genes, which ...
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 385 (1997), S. 525-529 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Immunocytochemistry was performed on frozen sections of mouse ovaries to investigate the composition of oocyte-granulosa cell gap junctions. Antibodies specific for connexins (Cx) 37,40 and 43 were used because their messenger RNAs had been previously detected in ovary6"8. Anti-Cx37 antibodies9 ...
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1572-9346
    Keywords: complex adaptive system ; organizational learning ; genetic algorithm ; resource allocation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract A framework for and a computational model of organizational behavior based on an artificial adaptive system (AAS) is presented. An AAS, a modeling approach based on genetic algorithms, enables the modeling of organizational learning and adaptability. This learning can be represented as decisions to allocate resources to the higher performing organizational agents (i.e., individuals, groups, departments, or processes, depending on the level of analysis) critical to the organization's survival in different environments. Adaptability results from the learning function enabling the organizations to change as the environment changes. An AAS models organizational behavior from a micro-unit perspective, where organizational behavior is a function of the aggregate actions and interactions of each of the individual agents of which the organization is composed. An AAS enables organizational decision making in a dynamic environment to be modeled as a satisficing process and not as a maximization process. To demonstrate the feasibility and usefulness of such an approach, a financial trading adaptive system (FTAS) organization is computationally modeled based on the AAS framework. An FTAS is an example of how the learning mechanism in an AAS can be used to allocate resources to critical individuals, processes, functions, or departments within an organization.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1572-8595
    Keywords: animal models ; electrophysiology ; arrhythmias ; connexin ; gap junction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Introduction: Gap junctions consist of connexin (Cx) proteins that enable electrical coupling of adjacent cells and propagation of action potentials. Cx40 is solely expressed in the atrium and His-Purkinje system. The purpose of this study was to evaluate atrioventricular (AV) conduction in mice with a homozygous deletion of Connexin40 (Cx40−/−). Methods: Surface ECGs, intracardiac electrophysi-ology (EP) studies, and ambulatory telemetry were performed in Cx40−/− mutant mice and wild-type (WT) controls. Atrioventricular (AV) conduction parameters and arrhythmia inducibility were evaluated using programmed stimulation. Analysis of heart rate variability was based on results of ambulatory monitoring. Results: Significant findings included prolonged measures of AV refractoriness and conduction in connexin40-deficient mice, including longer PR, AH, and HV intervals, increased AV refractory periods, and increased AV Wenckebach and 2:1 block cycle lengths. Connexin40-deficient mice also had an increased incidence of inducible ventricular tachycardia, decreased basal heart rates, and increased heart rate variability. Conclusion: A homozygous disruption of Cx40 results in prolonged AV conduction parameters due to abnormal electrical coupling in the specialized conduction system, which may also predispose to arrhythmia vulnerability.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0568
    Keywords: Gap junction ; Connexin26 ; Rat Cochlea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gap junctions in the rat cochlea were investigated using immunostaining for connexin26 and transmission electron microscopy. Electron microscopy of normal and pre-embedded immunostained material showed that there were gap junctions between and among all cells that light microscopy showed to have immunostained appositions. Light microscopy showed immunostaining between and among all cell types that electron microscopy showed to be joined by gap junctions. Immunostaining for connexin26 was therefore taken as providing a reasonable approximation of the locations of gap junctions throughout the cochlea and was used to provide an overview of the extent of those locations. Cells interconnected via gap junctions fell into one of two groups. The first group consists of nonsensory epithelial cells and includes interdental cells of the spiral limbus, inner sulcus cells, organ of Corti supporting cells, outer sulcus cells, and cells within the root processes of the spiral ligament. The second group consists of connective tissue cells and includes various fibrocyte types of the spiral limbus and spiral ligament, basal and intermediate cells of the stria vascularis, and mesenchymal cells which line the scala vestibuli. The present work represents a first attempt towards a description of how serial gap junctions among cochlear cells reflect a level of organization of the tissue. The organization described here, together with a great deal of information from previous investigators, suggest that serially arranged gap junctions of both epithelial and connective tissue cells serve as the strucural basis for recycling endolymphatic potassium ions that pass through the sensory cells during the transduction process.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 371 (1994), S. 208-209 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] SIR - Connexins (Cx) oligomerize into channels (called connexons) that span a single plasma membrane. Connexons in adjacent cells align to form complete intercellular channels that are sensitive to the voltage difference between the cytoplasms of the coupled cells. Because the intercellular channel ...
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