Hemichannels; from the molecule to the function
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...
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2021
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| _version_ | 1869529190950240256 |
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| author | Mauricio Antonio Retamal Juan C. Saez |
| author_browse | Juan C. Saez Mauricio Antonio Retamal |
| author_facet | Mauricio Antonio Retamal Juan C. Saez |
| author_sort | Mauricio Antonio Retamal |
| collection | Directory of Open Access Books |
| description | 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. |
| format | Online |
| id | doab-20.500.12854ir-49197 |
| institution | Directory of Open Access Books |
| language | eng |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Frontiers Media SA |
| publisherStr | Frontiers Media SA |
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| spelling | doab-20.500.12854ir-491972024-03-31T22:45:15Z Hemichannels; from the molecule to the function Mauricio Antonio Retamal Juan C. Saez QP1-981 Q1-390 redox regulation posttranslational modifications gap junction channels pannexins hemichannels Connexins thema EDItEUR::M Medicine and Nursing::MF Pre-clinical medicine: basic sciences::MFG Physiology 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. 2021-02-11T15:11:44Z 2021-02-11T15:11:44Z 2016-03-10 08:14:32 2015 book 18718 16648714 9782889194674 https://directory.doabooks.org/handle/20.500.12854/49197 eng Frontiers Research Topics image/jpeg Attribution 4.0 International http://www.frontiersin.org/books/Hemichannels;_from_the_molecule_to_the_function_/499 http://journal.frontiersin.org/researchtopic/1930/hemichannels-from-the-molecule-to-the-function Frontiers Media SA 10.3389/978-2-88919-467-4 10.3389/978-2-88919-467-4 bf5ce210-e72e-4860-ba9b-c305640ff3ae 9782889194674 122 open access |
| spellingShingle | QP1-981 Q1-390 redox regulation posttranslational modifications gap junction channels pannexins hemichannels Connexins thema EDItEUR::M Medicine and Nursing::MF Pre-clinical medicine: basic sciences::MFG Physiology Mauricio Antonio Retamal Juan C. Saez Hemichannels; from the molecule to the function |
| title | Hemichannels; from the molecule to the function |
| title_full | Hemichannels; from the molecule to the function |
| title_fullStr | Hemichannels; from the molecule to the function |
| title_full_unstemmed | Hemichannels; from the molecule to the function |
| title_short | Hemichannels; from the molecule to the function |
| title_sort | hemichannels from the molecule to the function |
| topic | QP1-981 Q1-390 redox regulation posttranslational modifications gap junction channels pannexins hemichannels Connexins thema EDItEUR::M Medicine and Nursing::MF Pre-clinical medicine: basic sciences::MFG Physiology |
| topic_facet | QP1-981 Q1-390 redox regulation posttranslational modifications gap junction channels pannexins hemichannels Connexins thema EDItEUR::M Medicine and Nursing::MF Pre-clinical medicine: basic sciences::MFG Physiology |
| url | 18718 |
| work_keys_str_mv | AT mauricioantonioretamal hemichannelsfromthemoleculetothefunction AT juancsaez hemichannelsfromthemoleculetothefunction |