Increasing Gap Junctional Coupling: A Tool for Dissecting the Role of Gap Junctions

AbstractTumour development is a process resulting from the disturbance of various cellular functions including cell proliferation, adhesion and motility. While the role of these cell parameters in tumour promotion and progression has been widely recognized, the mechanisms that influence gap junctional coupling during tumorigenesis remain elusive. Neoplastic cells usually display decreased levels of connexin expression and/or gap junctional coupling. Thus, impaired intercellular communication via gap junctions may facilitate the release of a potentially neoplastic cell from the controlling regime of the surrounding tissue, leading to tumour promotion. However, recent data indicates that metastatic tumour cell lines are often characterized by relatively high levels of connexin expression and gap junctional coupling. This review outlines current knowledge on the role of connexins in tumorigenesis and the possible mechanisms of the interference of gap junctional coupling with the processes of tumour invasion and metastasis.

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Connexins and steroidogenesis in mouse Leydig cells

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2012-0385 ◽

2013 ◽

Vol 91 (2) ◽

pp. 157-164 ◽

Cited By ~ 11

Author(s):

Dan Li ◽

Poonampreet Sekhon ◽

Kevin J. Barr ◽

Lucrecia Márquez-Rosado ◽

Paul D. Lampe ◽

...

Keyword(s):

Gap Junctions ◽

Leydig Cell ◽

Leydig Cells ◽

Adult Mouse ◽

Chain Reaction ◽

Junctional Coupling ◽

Polymerase Chain ◽

Gap Junctional ◽

Gap Junctional Coupling

Connexin43 has been recognized as forming gap junctions in Leydig cells. However, previous work has shown that mouse Leydig cells lacking this connexin do not suffer any limitation of their ability to produce testosterone when stimulated with luteinizing hormone. The objective of this study was to identify additional connexins in mouse Leydig cells that could be required for steroidogenesis. A reverse transcription – polymerase chain reaction screen involving isolated adult Leydig cells identified connexin36 and connexin45 as expressed along with connexin43. Treatment of dissociated testes with carbenoxolone, a nonspecific blocker of gap junctional coupling, significantly reduced testosterone output as did treatment with quinine, which disrupts coupling provided by connexin36 and connexin45 gap junctions but not those composed of connexin43, indicating that either or both of connexins 36 and 45 could be involved in supporting Leydig cell steroidogenesis. Immunolabeling of adult mouse testis sections confirmed the localization of connexin36 along with connexin43 in Leydig cell gap junctions but not connexin45, which is distributed throughout the cells. It was concluded that connexin36, connexin43, and connexin45 are coexpressed in Leydig cells with connexins 36 and 43 contributing to gap junctions. The role of connexin45 remains to be elucidated.

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Bursting in Inhibitory Interneuronal Networks: A Role for Gap-Junctional Coupling

Journal of Neurophysiology ◽

10.1152/jn.1999.81.3.1274 ◽

1999 ◽

Vol 81 (3) ◽

pp. 1274-1283 ◽

Cited By ~ 90

Author(s):

F. K. Skinner ◽

L. Zhang ◽

J. L. Perez Velazquez ◽

P. L. Carlen

Keyword(s):

Theoretical Work ◽

Oscillatory Behavior ◽

Minimal Network ◽

Junctional Coupling ◽

Synchronization Mechanisms ◽

The Individual ◽

Gap Junctional ◽

Gap Junctional Coupling ◽

Inhibitory Networks

Bursting in inhibitory interneuronal networks: a role for gap-junctional coupling. Much work now emphasizes the concept that interneuronal networks play critical roles in generating synchronized, oscillatory behavior. Experimental work has shown that functional inhibitory networks alone can produce synchronized activity, and theoretical work has demonstrated how synchrony could occur in mutually inhibitory networks. Even though gap junctions are known to exist between interneurons, their role is far from clear. We present a mechanism by which synchronized bursting can be produced in a minimal network of mutually inhibitory and gap-junctionally coupled neurons. The bursting relies on the presence of persistent sodium and slowly inactivating potassium currents in the individual neurons. Both GABAA inhibitory currents and gap-junctional coupling are required for stable bursting behavior to be obtained. Typically, the role of gap-junctional coupling is focused on synchronization mechanisms. However, these results suggest that a possible role of gap-junctional coupling may lie in the generation and stabilization of bursting oscillatory behavior.

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Ca2+ regulation of gap junctional coupling in lens epithelial cells

AJP Cell Physiology ◽

10.1152/ajpcell.2001.281.3.c972 ◽

2001 ◽

Vol 281 (3) ◽

pp. C972-C981 ◽

Cited By ~ 24

Author(s):

Grant C. Churchill ◽

Monica M. Lurtz ◽

Charles F. Louis

Keyword(s):

Epithelial Cells ◽

Gap Junctions ◽

Direct Action ◽

Hill Coefficient ◽

Lens Epithelial Cells ◽

Alexa Fluor ◽

Agonist Stimulation ◽

Junctional Coupling ◽

Gap Junctional ◽

Gap Junctional Coupling

The quantitative effects of Ca2+signaling on gap junctional coupling in lens epithelial cells have been determined using either the spread of Mn2+ that is imaged by its ability to quench the fluorescence of fura 2 or the spread of the fluorescent dye Alexa Fluor 594. Gap junctional coupling was unaffected by a mechanically stimulated cell-to-cell Ca2+wave. Furthermore, when cytosolic Ca2+ concentration (Ca[Formula: see text]) increased after the addition of the agonist ATP, coupling was unaffected during the period that Ca[Formula: see text] was maximal. However, coupling decreased transiently ∼5–10 min after agonist addition when Ca[Formula: see text] returned to resting levels, indicating that this transient decrease in coupling was unlikely due to a direct action of Ca[Formula: see text] on gap junctions. An increase in Ca[Formula: see text] mediated by the ionophore ionomycin that was sustained for several minutes resulted in a more rapid and sustained decrease in coupling (IC50 ∼300 nM Ca2+, Hill coefficient of 4), indicating that an increase in Ca[Formula: see text]alone could regulate gap junctions. Thus Ca[Formula: see text]increases that occurred during agonist stimulation and cell-to-cell Ca2+ waves were too transient to mediate a sustained uncoupling of lens epithelial cells.

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Gap junctional coupling and connexin immunoreactivity in rabbit retinal glia

Visual Neuroscience ◽

10.1017/s0952523806231018 ◽

2006 ◽

Vol 23 (1) ◽

pp. 1-10 ◽

Cited By ~ 17

Author(s):

KATHLEEN R. ZAHS ◽

PAUL W. CEELEN

Keyword(s):

Gap Junctions ◽

Gap Junction ◽

Lucifer Yellow ◽

Müller Cells ◽

Müller Cell ◽

Muller Cells ◽

Junctional Coupling ◽

Muller Cell ◽

Gap Junctional ◽

Gap Junctional Coupling

Gap junctions provide a pathway for the direct intercellular exchange of ions and small signaling molecules. Gap junctional coupling between retinal astrocytes and between astrocytes and Müller cells, the principal glia of vertebrate retinas, has been previously demonstrated by the intercellular transfer of gap-junction permeant tracers. However, functional gap junctions have yet to be demonstrated between mammalian Müller cells. In the present study, when the gap-junction permeant tracers Neurobiotin and Lucifer yellow were injected into a Müller cellviaa patch pipette, the tracers transferred to at least one additional cell in more than half of the cases examined. Simultaneous whole-cell recordings from pairs of Müller cells in the isolated rabbit retina revealed electrical coupling between closely neighboring cells, confirming the presence of functional gap junctions between rabbit Müller cells. The limited degree of this coupling suggests that Müller cell–Müller cell gap junctions may coordinate the functions of small ensembles of these glial cells. Immunohistochemistry and immunoblotting were used to identify the connexins in rabbit retinal glia. Connexin30 (Cx30) and connexin43 (Cx43) immunoreactivities were associated with astrocytes in the medullary ray region of the retinas of both pigmented and albino rabbits. Connexin43 was also found in Müller cells, but antibody recognition differed between astrocytic and Müller cell connexin43.

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Effect of Variations in Gap Junctional Coupling on the Frequency of Oscillatory Action Potentials in a Smooth Muscle Syncytium

Frontiers in Physiology ◽

10.3389/fphys.2021.655225 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shailesh Appukuttan ◽

Keith L. Brain ◽

Rohit Manchanda

Keyword(s):

Gap Junctions ◽

Electrical Activity ◽

Action Potentials ◽

Protein Subunits ◽

Gating Kinetics ◽

Coupled Cells ◽

Junctional Coupling ◽

Gap Junctional ◽

Gap Junctional Coupling ◽

Kinetics Of

Gap junctions provide pathways for intercellular communication between adjacent cells, allowing exchange of ions and small molecules. Based on the constituent protein subunits, gap junctions are classified into different subtypes varying in their properties such as unitary conductances, sensitivity to transjunctional voltage, and gating kinetics. Gap junctions couple cells electrically, and therefore the electrical activity originating in one cell can affect and modulate the electrical activity in adjacent cells. Action potentials can propagate through networks of such electrically coupled cells, and this spread is influenced by the nature of gap junctional coupling. Our study aims to computationally explore the effect of differences in gap junctional properties on oscillating action potentials in electrically coupled tissues. Further, we also explore variations in the biophysical environment by altering the size of the syncytium, the location of the pacemaking cell, as well as the occurrence of multiple pacemaking cells within the same syncytium. Our simulation results suggest that the frequency of oscillations is governed by the extent of coupling between cells and the gating kinetics of different gap junction subtypes. The location of pacemaking cells is found to alter the syncytial behavior, and when multiple oscillators are present, there exists an interplay between the oscillator frequency and their relative location within the syncytium. Such variations in the frequency of oscillations can have important implications for the physiological functioning of syncytial tissues.

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