Search results: Found 2

Listing 1 - 2 of 2
Sort by
Hemichannels; from the molecule to the function

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194674 Year: Pages: 122 DOI: 10.3389/978-2-88919-467-4 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
License:

Loading...
Export citation

Choose an application

Abstract

Coordinated cell interactions are required to accomplish several complex and dynamic tasks observed in several tissues. Cell function may be coordinated by cell-to-cell communication through gap junctions channels (GJCs). These channels are formed by the serial docking of two hemichannels, which in turn are formed by six protein subunits called connexins (Cxs). It is well known that GJCs are involved in several functions, such as intercellular propagation of calcium waves, spread of electrotonic potentialsand spatial buffering of ions and metabolites. On the other hand, undocked hemichannels, which are not forming GJCs, can also serve other functions as “free hemichannels”. Currently, it is recognized that undocked hemichannels may have functional relevance in cell physiology allowing diffusional exchange of ions and small molecules between intra- and extra-cellular compartments. Additionally, another family of proteins calls pannexins (Panx) also forms functional hemichannels at the plasma membrane. Recently, Panxhemichannels have been involved in both pathological and physiological processes. Controlled hemichannel opening allows the release of small signaling molecules including ATP, glutamate, NAD+, adenosine, cyclic nucleotides, PGE2. They also allow uptake of relevant signaling molecules (e.g., cADPR) and metabolites (e.g., glucose). Additionally, a growing body of evidence shows that hemichannels are involved in important processes, such glucose detection in tanicytes, activation of the inflammasome, memory consolidation in the basolateral amygdala, potentiation of muscle contraction and release of nitric oxide from endothelial cells, among others. However, hemichannels can also play an important role in the homeostatic imbalance observed in diverse chronic diseases. In fact, massive and/or uncontrolled hemichannel opening induces or accelerates cell death in several pathological conditions including Charcot-Marie-Tooth disease, ischemia, oculodentodigital dysplasia, hydrotic ectodermic dysplasia, inflammatory responses, and deafness. Hemichannel-mediated cell death is due mainly to an entry of Ca+2. The latter activates proteases, nucleases and lipases, causing irreversible cell damage. An increasing amount of evidence demonstrates that blockade of uncontrolled hemichannel opening greatly reduces the cellular damage observed in several chronic diseases models. Therefore, Cx and Panx-hemichannels appear as promising drug targets for clinical treatment of human chronic diseases. Therefore, pharmacological tools are urgently needed to further elucidate hemichannels functions and to validate them as drug targets for the development of novel therapies for connexin-based diseases. Thus, understanding the role of Cx and Panx-hemichannels under physiological conditions and recognizing the molecular mechanisms controlling them, may provide us with a better picture of the hemichannels participation in some diseases and of the signals underlying their malfunctioning.

Mind the gap! Gap junction channels and their importance in pathogenesis

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192380 Year: Pages: 252 DOI: 10.3389/978-2-88919-238-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Medicine (General) --- Therapeutics --- Science (General)
Added to DOAB on : 2015-11-16 15:44:59
License:

Loading...
Export citation

Choose an application

Abstract

"Cells live together, but die singly", this sentence wrote the German physiologist Theodor Engelmann in 1875 and although he had no particular knowledge of gap junction channels (their structure was discovered around 100 years later) he described their functions very well: gap junction channels are essential for intercellular communication and crucial for the development of tissue and organs. But besides providing an opportunity for cells to communicate gap junction channels might also prevent intercellular communication by channel closure thereby preserving the surrounding healthy tissue in case of cellular necrosis. According to today’s understanding gap junction channels play an important role during embryonic development, during growth, wound healing and cell differentiation and are also involved in the process of learning. In the past decades most intensive research was done not only to unravel the physiological role of gap junction channels but also to extend our knowledge of the contribution of these channels in pathogenesis. A new frontier emerges in the field "pharmacology of gap junctions" with the aim to control growth, differentiation, or electrical coupling via targeting gap junction channels pharmacologically. As we know today disturbances in gap junction synthesis, assembly and cellular distribution may account for various organic disorders from most different medical fields, such as the Charcot-Marie-Tooth neuropathy, epilepsy, Chagas-disease, Naxos-syndrome, congenital cardiac malformations, arrhythmias, cancer and as a very common disease in industrial countries atherosclerosis. Point mutations in gap junction channels have been found to cause hereditary diseases like the congenital deafness or the Charcot-Marie-Tooth neuropathy but the exact molecular mechanisms of gap junction malfunction from most of the mentioned illnesses are not fully understood. Moreover, in the last few years research has expanded on the role and function of connexin hemichannels and on a relatively new field the pannexins. The purpose of this volume is to give a comprehensive overview of the involvement of gap junction channels, hemichannels and pannexins on pathogenesis of inborn and acquired diseases and on emerging pharmacological strategies to target these channels. We welcome our colleagues to contribute their findings on the influence of gap junctions on pathogenesis and to unravel the secrets of intercellular communication. Take the lid off!

Listing 1 - 2 of 2
Sort by
Narrow your search

Publisher

Frontiers Media SA (2)


License

CC by (2)


Language

english (2)


Year
From To Submit

2015 (1)

2014 (1)

-->