scholarly journals Connexin36 Gap Junction Blockade Is Ineffective at Reducing Seizure-Like Event Activity in Neocortical Mouse Slices

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Logan J. Voss ◽  
Noortje Mutsaerts ◽  
James W. Sleigh
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Population Activity ◽  
Low Magnesium ◽  
Artificial Cerebrospinal Fluid ◽  
Seizure Models ◽  
Neocortical Slice ◽  
Neocortical Seizures ◽  
Anticonvulsant Effects

Despite much research, there remains controversy over the role of gap junctions in seizure processes. Many studies report anticonvulsant effects of gap junction blockade, but contradictory results have also been reported. The aim of this study was to clarify the role of connexin36 (Cx36) gap junctions in neocortical seizures. We used the mouse neocortical slice preparation to investigate the effect of pharmacological (mefloquine) and genetic (Cx36 knockout mice (Cx36KO)) manipulation of Cx36 gap junctions on two seizure models: low-magnesium artificial cerebrospinal fluid (ACSF) and aconitine perfusion in low-magnesium ACSF. Low-magnesium- (nominally zero) and aconitine- (230 nM) induced seizure-like event (SLE) population activity was recorded extracellularly. The results were consistent in showing that neither mefloquine (25 μM) nor genetic knockdown of Cx36 expression had anticonvulsant effects on SLE activity generated by either method. These findings call into question the widely held idea that open Cx36 gap junctions promote seizure activity.

scholarly journals Gap junction networks in mushroom bodies participate in visual learning and memory in Drosophila

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Qingqing Liu ◽  
Xing Yang ◽  
Jingsong Tian ◽  
Zhongbao Gao ◽  
Meng Wang ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Learning And Memory ◽  
Visual Learning ◽  
Mushroom Bodies ◽  
Single Pair ◽  
Neural Information ◽  
Neural Information Processing ◽  
Coupling Approach

Gap junctions are widely distributed in the brains across species and play essential roles in neural information processing. However, the role of gap junctions in insect cognition remains poorly understood. Using a flight simulator paradigm and genetic tools, we found that gap junctions are present in Drosophila Kenyon cells (KCs), the major neurons of the mushroom bodies (MBs), and showed that they play an important role in visual learning and memory. Using a dye coupling approach, we determined the distribution of gap junctions in KCs. Furthermore, we identified a single pair of MB output neurons (MBONs) that possess a gap junction connection to KCs, and provide strong evidence that this connection is also required for visual learning and memory. Together, our results reveal gap junction networks in KCs and the KC-MBON circuit, and bring new insight into the synaptic network underlying fly’s visual learning and memory.

A non-connexon protein (MIP) is involved in eye lens gap-junction formation

1989 ◽  
Vol 93 (3) ◽  
pp. 509-513
Author(s):  
W.T. Gruijters
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Eye Lens ◽  
Specific Interactions ◽  
Domain Specific ◽  
Lens Fibre ◽  
Junction Formation ◽  
New Perspective

New immunolocalization data put the role of the lens MP26 (MIP) protein in a new perspective. During maturation of lens fibre cells, MIP is found to associate specifically with two structures, gap junctions and cell interlocking processes (known as ball and socket domains). It is significant that the zone in which these associations are most striking is discrete, coinciding with the zone of rapidly enlarging junctional plaques and newly forming ball and socket domains. Observation of domain-specific interactions of MIP with forming gap junctions and ball and socket domains suggests that MIP may be involved in the formation of close membrane appositions. Furthermore, previous ambiguities in the literature over the presence of MIP in gap junctions are clarified by the knowledge that, in situ, MIP associates strongly with gap junctions for only a brief period (with less than about 5% of all lens gap junctions at any one time) during the assembly of junctional plaques.

scholarly journals Decreased Fast Ripples in the Hippocampus of Rats with Spontaneous Recurrent Seizures Treated with Carbenoxolone and Quinine

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Consuelo Ventura-Mejía ◽  
Laura Medina-Ceja
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
High Frequency Oscillations ◽  
The Mean ◽  
Eeg Recordings ◽  
The Right ◽  
Spontaneous Recurrent Seizures

Background. In models of temporal lobe epilepsy and in patients with this pathology, high frequency oscillations called fast ripples (FRs, 250–600 Hz) can be observed. FRs are considered potential biomarkers for epilepsy and, in the light of manyin vitroandin silicostudies, we thought that electrical synapses mediated by gap junctions might possibly modulate FRsin vivo.Methods. Animals with spontaneous recurrent seizures induced by pilocarpine administration were implanted with movable microelectrodes in the right anterior and posterior hippocampus to evaluate the effects of gap junction blockers administered in the entorhinal cortex. The effects of carbenoxolone (50 nmoles) and quinine (35 pmoles) on the mean number of spontaneous FR events (occurrence of FRs), as well as on the mean number of oscillation cycles per FR event and their frequency, were assessed using a specific algorithm to analyze FRs in intracranial EEG recordings.Results. We found that these gap junction blockers decreased the mean number of FRs and the mean number of oscillation cycles per FR event in the hippocampus, both during and at different times after carbenoxolone and quinine administration.Conclusion. These data suggest that FRs may be modulated by gap junctions, although additional experimentsin vivowill be necessary to determine the precise role of gap junctions in this pathological activity associated with epileptogenesis.

scholarly journals Changes in gap junction expression and function following ischemic injury of spinal cord white matter

2014 ◽  
Vol 112 (9) ◽  
pp. 2067-2075 ◽  
Author(s):  
Karina Goncharenko ◽  
Eftekhar Eftekharpour ◽  
Alexander A. Velumian ◽  
Peter L. Carlen ◽  
Michael G. Fehlings
Keyword(s):  
Spinal Cord ◽  
White Matter ◽  
Gap Junctions ◽  
Gap Junction ◽  
Glucose Deprivation ◽  
Wistar Rat ◽  
Conduction Loss ◽  
Axonal Dysfunction

Gap junctions are widely present in spinal cord white matter; however, their role in modulating the dynamics of axonal dysfunction remains largely unexplored. We hypothesized that inhibition of gap junctions reduces the loss of axonal function during oxygen and glucose deprivation (OGD). The functional role of gap junctions was assessed by electrophysiological recordings of compound action potentials (CAPs) in Wistar rat spinal cord slices with the sucrose gap technique. The in vitro slices were subjected to 30-min OGD. Gap junction connexin (Cx) mRNA expression was determined by qPCR and normalized to β-actin. A 30-min OGD resulted in reduction of CAPs to 14.8 ± 4.6% of their pre-OGD amplitude ( n = 5). In the presence of gap junction blockers carbenoxolone (Cbx; 100 μM) and 1-octanol (Oct; 300 μM), the CAP reduction in OGD was to only 35.7 ± 5.7% of pre-OGD amplitude in Cbx ( n = 9) and to 37.4 ± 8.9% of pre-OGD amplitude in Oct ( n = 10). Both drugs also noticeably prolonged the half-decline time of CAP amplitudes in OGD from 6.0 min in no-drug conditions to 9.6 min in the presence of Cbx and to 7.7 min in the presence of Oct, suggesting that blocking gap junctions reduces conduction loss during OGD. With application of Cbx and Oct in the setting of OGD, expression of Cx30 and Cx43 mRNA was downregulated. Our data provide new insights into the role of gap junctions in white matter ischemia and reveal the necessity of a cautious approach in determining detrimental or beneficial effects of gap junction blockade in white matter ischemia.

scholarly journals Connexin 43 Expression on Peripheral Blood Eosinophils: Role of Gap Junctions in Transendothelial Migration

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Harissios Vliagoftis ◽  
Cory Ebeling ◽  
Ramses Ilarraza ◽  
Salahaddin Mahmudi-Azer ◽  
Melanie Abel ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Peripheral Blood ◽  
Connexin 43 ◽  
Transendothelial Migration ◽  
Glycyrrhetinic Acid ◽  
Dependent Manner ◽  
Dye Transfer ◽  
Blood Eosinophils

Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx)43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

scholarly journals Lens Gap Junctions in Growth, Differentiation, and Homeostasis

2010 ◽  
Vol 90 (1) ◽  
pp. 179-206 ◽  
Author(s):  
Richard T. Mathias ◽  
Thomas W. White ◽  
Xiaohua Gong
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Transport Systems ◽  
Ion Flow ◽  
Ion Concentrations ◽  
Gap Junction Channels ◽  
Growth Development

The cells of most mammalian organs are connected by groups of cell-to-cell channels called gap junctions. Gap junction channels are made from the connexin (Cx) family of proteins. There are at least 20 isoforms of connexins, and most tissues express more than 1 isoform. The lens is no exception, as it expresses three isoforms: Cx43, Cx46, and Cx50. A common role for all gap junctions, regardless of their Cx composition, is to provide a conduit for ion flow between cells, thus creating a syncytial tissue with regard to intracellular voltage and ion concentrations. Given this rather simple role of gap junctions, a persistent question has been: Why are there so many Cx isoforms and why do tissues express more than one isoform? Recent studies of lens Cx knockout (KO) and knock in (KI) lenses have begun to answer these questions. To understand these roles, one must first understand the physiological requirements of the lens. We therefore first review the development and structure of the lens, its numerous transport systems, how these systems are integrated to generate the lens circulation, the roles of the circulation in lens homeostasis, and finally the roles of lens connexins in growth, development, and the lens circulation.

Structure of the Ductin Channel

1998 ◽  
Vol 18 (6) ◽  
pp. 287-297 ◽  
Author(s):  
Malcolm E. Finbow ◽  
John D. Pitts
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Cell Movement ◽  
Large Family ◽  
Structural Data ◽  
Proton Pumps ◽  
Gap Junction Channel ◽  
Essential Components ◽  
Resolution Model

Gap junctions appear to be essential components of metazoan animals providing a means of direct means of communication between neighboring cells. They are sieve-like structures which allow cell–cell movement of cytosolic solutes below 1000 MW. The major role of gap junctions would appear to be homeostatic giving rise to groups of cells which act as functional units. Ductin is the major core component of gap junctions and recent structural data shows it to be a four alpha-helical bundle which fits particularly well into a low resolution model of the gap junction channel. Ductin is also the main membrane component of the vacuolar H+-ATPase that is found in all eukaryotes and it seems likely that the gap junction channel first evolved as a housing for the rotating spindle of these proton pumps. Because ductin protrudes little from the membrane, other proteins are required to bring cell surfaces close enough together to form gap junctions. Such proteins may include connexins, a large family of proteins found in vertebrates.

Gap Junctions Involvement in Brain Hyperexcitability Phenomena

2008 ◽  
Vol 59 (11) ◽  
Author(s):  
Doru-Georg Margineanu
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Intercellular Communication ◽  
Experimental Models ◽  
Mammalian Brain ◽  
Cx43 Expression ◽  
Medical Need ◽  
Brain Hyperexcitability ◽  
Models Of Epilepsy ◽  
Anticonvulsant Effects

Hyperexcitability pathologies, epitomized by epilepsy, are a largely unmet medical need, asking for conceptual developments on the functioning of networks of inter-communicating neurons and glia. Intercellular communication via gap junction (GJ) channels is largely present in mammalian brain. The GJ channels are made of proteins, essentially the connexins (Cxs) widely expressed in brain and in peripheral organs, the most abundant being Cx43. Expression level of Cx43 appears elevated in epileptic brains. Many different compounds actually modify the strength of GJ intercellular communication, though none is specific for GJs. Reference GJ blockers have anticonvulsant effects in numerous experimental models of epilepsy and some data suggest that GJ blockade might specifically act on epileptic hyper-synchrony, a feature hardly targeted by current antiepileptic drugs. The involvement of GJs in migraine is also suggested by recent results.

scholarly journals Astroglial connexins and cognition: memory formation or deterioration?

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Jin-Ting He ◽  
Xiao-Yan LI ◽  
Le Yang ◽  
Xin Zhao
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Connexin 43 ◽  
Memory Formation ◽  
Gap Junction Communication ◽  
Different Types ◽  
Excessive Activation ◽  
High Conductance ◽  
Junction Proteins

Abstract Connexins are the membrane proteins that form high-conductance plasma membrane channels and are the important constituents of gap junctions and hemichannels. Among different types of connexins, connexin 43 is the most widely expressed and studied gap junction proteins in astrocytes. Due to the key involvement of astrocytes in memory impairment and abundant expression of connexins in astrocytes, astroglial connexins have been projected as key therapeutic targets for Alzheimer’s disease. On the other hand, the role of connexin gap junctions and hemichannels in memory formation and consolidation has also been reported. Moreover, deletion of these proteins and loss of gap junction communication result in loss of short-term spatial memory. Accordingly, both memory formation and memory deteriorating functions of astrocytes-located connexins have been documented. Physiologically expressed connexins may be involved in the memory formation, while pathologically increased expression of connexins with consequent excessive activation of astrocytes may induce neuronal injury and cognitive decline. The present review describes the memory formation as well as memory deteriorating functions of astroglial connexins in memory disorders of different etiology with possible mechanisms.

Connexin 43 ubiquitination determines the fate of gap junctions: restrict to survive

2015 ◽  
Vol 43 (3) ◽  
pp. 471-475 ◽  
Author(s):  
Teresa M. Ribeiro-Rodrigues ◽  
Steve Catarino ◽  
Maria J. Pinho ◽  
Paulo Pereira ◽  
Henrique Girao
Keyword(s):  
Plasma Membrane ◽  
Gap Junctions ◽  
Gap Junction ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Transmembrane Proteins ◽  
Post Translational Modifications ◽  
Gap Junction Intercellular Communication

Connexins (Cxs) are transmembrane proteins that form channels which allow direct intercellular communication (IC) between neighbouring cells via gap junctions. Mechanisms that modulate the amount of channels at the plasma membrane have emerged as important regulators of IC and their de-regulation has been associated with various diseases. Although Cx-mediated IC can be modulated by different mechanisms, ubiquitination has been described as one of the major post-translational modifications involved in Cx regulation and consequently IC. In this review, we focus on the role of ubiquitin and its effect on gap junction intercellular communication.

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