scholarly journals Mechanisms Underlying Connexin Hemichannel Activation in Disease

2021 ◽  
Vol 22 (7) ◽  
pp. 3503
Author(s):  
Raf Van Campenhout ◽  
Ana Rita Gomes ◽  
Timo W.M. De Groof ◽  
Serge Muyldermans ◽  
Nick Devoogdt ◽  
...  
Keyword(s):  
Cell Death ◽  
Gap Junctions ◽  
Connexin Hemichannel ◽  
Extracellular Environment ◽  
Connexin Hemichannels

Gap junctions and connexin hemichannels mediate intercellular and extracellular communication, respectively. While gap junctions are seen as the “good guys” by controlling homeostasis, connexin hemichannels are considered as the “bad guys”, as their activation is associated with the onset and dissemination of disease. Open connexin hemichannels indeed mediate the transport of messengers between the cytosol and extracellular environment and, by doing so, fuel inflammation and cell death in a plethora of diseases. The present mini-review discusses the mechanisms involved in the activation of connexin hemichannels during pathology.

scholarly journals Purinergic responses of chondrogenic stem cells to dynamic loading

2013 ◽  
Vol 78 (12) ◽  
pp. 1865-1874 ◽  
Author(s):  
Ivana Gadjanski ◽  
Gordana Vunjak-Novakovic
Keyword(s):  
Stem Cells ◽  
Dynamic Loading ◽  
Lucifer Yellow ◽  
Atp Release ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Flufenamic Acid ◽  
Release Assay ◽  
Extracellular Environment ◽  
Connexin Hemichannels

In habitually loaded tissues, dynamic loading can trigger ATP (adenosine 5?- triphosphate) release to extracellular environment, and result in calcium signaling via ATP binding to purine P2 receptors1. In the current study we have compared purinergic responses (ATP release) of two types of cells: bovine chondrocytes (bCHs) and human mesenchymal stem cells (hMSC) that were encapsulated in agarose and subjected to dynamic loading. Both cell types were cultured under chondrogenic conditions, and their responses to loading were evaluated by ATP release assay in combination with connexin (Cx)-sensitive fluorescent dye (Lucifer Yellow - LY) and a Cx-hemichannel blocker (Flufenamic acid - FFA). In response to dynamic loading, chondrogenic hMSCs released significantly higher amounts of ATP (5-fold) in comparison to the bCHs early in culture (day 2). Triggering of LY uptake in the bCHs and hMSCs by dynamic loading implies opening of the Cx-hemichannels. However, the number of LY-positive cells in hMSC-constructs was 2.5-fold lower compared to the loaded bCH-constructs, suggesting utilization of additional mechanisms of ATP release. Cx-reactive sites were detected in both bCHs and hMSCs-constructs. FFA application led to reduced ATP release both in bCHs and hMSCs, which confirms the involvement of connexin hemichannels, with more prominent effects in bCHs than in hMSCs, further implying the existence of additional mechanism of ATP release in chondrogenic hMSCs. Taken together, these results indicate stronger purinergic response to dynamic loading of chondrogenic hMSCs than primary chondrocytes, by activation of connexin hemichannels and additional mechanisms of ATP release.

Calcium tsunamis: do astrocytes transmit cell death messages via gap junctions during ischemia?

10.1038/2147 ◽  
1998 ◽  
Vol 1 (6) ◽  
pp. 431-432 ◽  
Author(s):  
Samantha L. Budd ◽  
Stuart A. Lipton
Keyword(s):  
Cell Death ◽  
Gap Junctions

GAP JUNCTIONS AND CONNEXIN HEMICHANNELS UNDERPIN HAEMOSTASIS AND THROMBOSIS

Heart ◽  
2014 ◽  
Vol 100 (Suppl 4) ◽  
pp. A18.1-A18
Author(s):  
S Vaiyapuri ◽  
CI Jones ◽  
P Sasikumar ◽  
LA Moraes ◽  
MS Ali ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Connexin Hemichannels

scholarly journals Gap junctions and connexin hemichannels in the regulation of haemostasis and thrombosis

2015 ◽  
Vol 43 (3) ◽  
pp. 489-494 ◽  
Author(s):  
Sakthivel Vaiyapuri ◽  
Gagan D. Flora ◽  
Jonathan M. Gibbins
Keyword(s):  
Gap Junctions ◽  
Intercellular Communication ◽  
Heart Attack ◽  
Wound Repair ◽  
Future Directions ◽  
Tissue Responses ◽  
The Stability ◽  
And Control ◽  
Connexin Hemichannels

Platelets are involved in the maintenance of haemostasis but their inappropriate activation leads to thrombosis, a principal trigger for heart attack and ischaemic stroke. Although platelets circulate in isolation, upon activation they accumulate or aggregate together to form a thrombus, where they function in a co-ordinated manner to prevent loss of blood and control wound repair. Previous report (1) indicates that the stability and functions of a thrombus are maintained through sustained, contact-dependent signalling between platelets. Given the role of gap junctions in the co-ordination of tissue responses, it was hypothesized that gap junctions may be present within a thrombus and mediate intercellular communication between platelets. Therefore studies were performed to explore the presence and functions of connexins in platelets. In this brief review, the roles of hemichannels and gap junctions in the control of thrombosis and haemostasis and the future directions for this research will be discussed.

scholarly journals Analysing Intercellular Communication in Astrocytic Networks Using “Astral”

2021 ◽  
Vol 15 ◽  
Author(s):  
Egor Dzyubenko ◽  
Wojciech Prazuch ◽  
Matthias Pillath-Eilers ◽  
Joanna Polanska ◽  
Dirk M. Hermann
Keyword(s):  
Gap Junctions ◽  
Intercellular Communication ◽  
Calcium Imaging ◽  
Systematic Investigation ◽  
Spontaneous Generation ◽  
Analysis Tool ◽  
The Novel ◽  
Imaging Data ◽  
Neuronal Interactions ◽  
Connexin Hemichannels

Astrocytic networks are critically involved in regulating the activity of neuronal networks. However, a comprehensive and ready-to-use data analysis tool for investigating functional interactions between the astrocytes is missing. We developed the novel software package named “Astral” to analyse intercellular communication in astrocytic networks based on live-cell calcium imaging. Our method for analysing calcium imaging data does not require the assignment of regions of interest. The package contains two applications: the core processing pipeline for detecting and quantifying Ca++ events, and the auxiliary visualization tool for controlling data quality. Our method allows for the network-wide quantification of Ca++ events and the analysis of their intercellular propagation. In a set of proof-of-concept experiments, we examined Ca++ events in flat monolayers of primary astrocytes and confirmed that inter-astrocytic interactions depend on the permeability of gap junctions and connexin hemichannels. The Astral tool is particularly useful for studying astrocyte-neuronal interactions on the network level. We demonstrate that compared with purely astrocytic cultures, spontaneous generation of Ca++ events in astrocytes that were co-cultivated with neurons was significantly increased. Interestingly, the increased astrocytic Ca++ activity after long-term co-cultivation with neurons was driven by the enhanced formation of gap junctions and connexin hemichannels but was not affected by silencing neuronal activity. Our data indicate the necessity for systematic investigation of astrocyte-neuronal interactions at the network level. For this purpose, the Astral software offers a powerful tool for processing and quantifying calcium imaging data.

scholarly journals Gap Junctions Mediate Bystander Cell Death in Developing Retina

2003 ◽  
Vol 23 (16) ◽  
pp. 6413-6422 ◽  
Author(s):  
Karen Cusato ◽  
Alejandra Bosco ◽  
Renato Rozental ◽  
Cinthya A. Guimarães ◽  
Benjamin E. Reese ◽  
...  
Keyword(s):  
Cell Death ◽  
Gap Junctions ◽  
Bystander Cell ◽  
Bystander Cell Death

scholarly journals Regulation of Connexin Hemichannels by Monovalent Cations

2005 ◽  
Vol 127 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Miduturu Srinivas ◽  
D. Paola Calderon ◽  
Jack Kronengold ◽  
Vytas K. Verselis
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Divalent Cations ◽  
Signaling Molecules ◽  
Primary Effect ◽  
Monovalent Cations ◽  
Modest Increase ◽  
Monovalent Ions ◽  
The Difference ◽  
Connexin Hemichannels

Opening of connexin hemichannels in the plasma membrane is highly regulated. Generally, depolarization and reduced extracellular Ca2+ promote hemichannel opening. Here we show that hemichannels formed of Cx50, a principal lens connexin, exhibit a novel form of regulation characterized by extraordinary sensitivity to extracellular monovalent cations. Replacement of extracellular Na+ with K+, while maintaining extracellular Ca2+ constant, resulted in >10-fold potentiation of Cx50 hemichannel currents, which reversed upon returning to Na+. External Cs+, Rb+, NH4+, but not Li+, choline, or TEA, exhibited a similar effect. The magnitude of potentiation of Cx50 hemichannel currents depended on the concentration of extracellular Ca2+, progressively decreasing as external Ca2+ was reduced. The primary effect of K+ appears to be a reduction in the ability of Ca2+, as well as other divalent cations, to close Cx50 hemichannels. Cx46 hemichannels exhibited a modest increase upon substituting Na+ with K+. Analyses of reciprocal chimeric hemichannels that swap NH2- and COOH-terminal halves of Cx46 and Cx50 demonstrate that the difference in regulation by monovalent ions in these connexins resides in the NH2-terminal half. Connexin hemichannels have been implicated in physiological roles, e.g., release of ATP and NAD+ and in pathological roles, e.g., cell death through loss or entry of ions and signaling molecules. Our results demonstrate a new, robust means of regulating hemichannels through a combination of extracellular monovalent and divalent cations, principally Na+, K+, and Ca2+.

scholarly journals Primary Osteocyte Supernatants Metabolomic Profiling of Two Transgenic Mice With Connexin43 Dominant Negative Mutants

2021 ◽  
Vol 12 ◽  
Author(s):  
Meng Chen ◽  
Guobin Li ◽  
Lan Zhang ◽  
Kaiting Ning ◽  
Baoqiang Yang ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Bone Cells ◽  
Dominant Negative ◽  
Regulatory Function ◽  
Metabolomic Profiling ◽  
Oxidative Stress Pathway ◽  
Liquid Chromatography Tandem Mass ◽  
Cx 43 ◽  
Fatty Acyls ◽  
Extracellular Environment

Osteocytes could release some small molecules (≤ 1 kDa) through gap junctions and hemichannels to extracellular environment, such as prostaglandin E2 (PGE2), nitric oxide (NO) and adenosine triphosphate (ATP), which play key roles in transferring signals between bone cells and other tissue cells. Connexin (Cx) 43 is the most abundant connexin in osteocytes. To further discover molecules released by osteocytes through Cx43 channels and better understand the regulatory function of Cx43 channels in osteocytes, we performed non-targeted global metabolomics analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) on conditioned medium collected from osteocytes isolated from two transgenic mouse models with Cx43 dominant negative mutants driven by a 10 kb-DMP1 promoter: R76W (gap junctions are blocked, whereas hemichannels are promoted) and Δ130-136 (both gap junctions and hemichannels are blocked). The results revealed that several new categories of molecules, such as “fatty acyls” and “carboxylic acids and derivatives”, could be released through osteocytic Cx43 channels. In addition, alteration of Cx43 channel function affected the release of metabolites related to inflammatory reaction and oxidative stress. Pathway analysis further showed that citric acid cycle was the most differential metabolic pathway regulated by Cx43 channels. In sum, these results isolated new potential metabolites released by osteocytes through Cx43 channels, and offered a novel perspective to understand the regulatory mechanisms of osteocytes on themselves and other cells as well.

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