Hemichannels; from the molecule to the function

Hemichannels; from the molecule to the function PDF Author: Mauricio Antonio Retamal
Publisher: Frontiers Media SA
ISBN: 2889194671
Category : Connexins
Languages : en
Pages : 123

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Book 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.

Hemichannels; from the molecule to the function

Hemichannels; from the molecule to the function PDF Author: Mauricio Antonio Retamal
Publisher: Frontiers Media SA
ISBN: 2889194671
Category : Connexins
Languages : en
Pages : 123

Get Book Here

Book 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.

Gap Junction Channels and Hemichannels

Gap Junction Channels and Hemichannels PDF Author: Taylor & Francis Group
Publisher: CRC Press
ISBN: 9780367658441
Category :
Languages : en
Pages : 289

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Book Description
Gap junction channels are a group of intercellular channels expressed in tissues and organs to synchronize many physiological processes. A gap junction channel is formed by the docking of two hemichannels, and each hemichannel is a hexamer of connexins. The field of gap junction channel and hemichannel research has recently exploded and became one of the most active areas of cell biology. Numerous novel approaches and techniques have been developed, but there is no single book dedicated to the unique techniques and protocols employed for the research on these large pore channels. This book fills the gap and focuses on protocols, approaches and reviews of gap junction channels and connexin hemichannels. It will be a useful reference for graduate students, postdoctoral fellows and researchers. Anyone with an interest in gap junction channels and hemichannels will need this summary of state-of-the-art techniques and protocols.

Gap Junctions: Molecular Basis of Cell Communication in Health and Disease

Gap Junctions: Molecular Basis of Cell Communication in Health and Disease PDF Author: Dale J. Benos
Publisher: Gulf Professional Publishing
ISBN: 9780125506458
Category : Medical
Languages : en
Pages : 692

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Book Description
Since the first gap junction protein (connexin) was cloned over a decade ago, more than a dozen connexin genes have been cloned. Consequently, a wealth of information on the molecular basis of gap junctional communication has been accumulated. This book pays tribute to this exciting era in the history of cell communication research by documenting the great strides made in this field as a result of the merging of biophysics and molecular biology, two of the most powerful approaches to studying the molecular basis of membrane channel behavior. Twenty-eight comprehensive chapters, authored by internationally recognized leaders in the field, discuss the biophysical, physiological, and molecular characteristics of cell-to-cell communication via gap junctions. Key aspects of molecular structure, formation, gating, conductance, and permeability of vertebrate and invertebrate gap junction channels are highlighted. In addition, a number of chapters focus on recent discoveries that implicate connexin mutations and alterations of gap junctional communication in the pathogenesis of several diseases, including the X-linked Charcot-Marie-Tooth demyelinating disease, some forms of inherited sensorineural deafness, malignant transformation, cardiac malformations and arrhythmia, eye lens cataract, and Chagas disease.

Intercellular Communication through Gap Junctions

Intercellular Communication through Gap Junctions PDF Author: Y. Kanno
Publisher: Newnes
ISBN: 0444599525
Category : Science
Languages : en
Pages : 474

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Book Description
Research on intercellular communication through gap junctions has continued to expand, and the meeting on which this book is based brought together many scientists from many different countries and disciplines. In line with the objective of the meeting, this volume focuses on the biological meaning of intercellular communication through gap junctions in various organs. The most recent up-to-date findings have been included in this extensive volume, valuable to all those interested in this rapidly expanding field.

Enteric Glia

Enteric Glia PDF Author: Brian D. Gulbransen
Publisher: Biota Publishing
ISBN: 1615046615
Category : Medical
Languages : en
Pages : 72

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Book Description
The enteric nervous system (ENS) is a complex neural network embedded in the gut wall that orchestrates the reflex behaviors of the intestine. The ENS is often referred to as the “little brain” in the gut because the ENS is more similar in size, complexity and autonomy to the central nervous system (CNS) than other components of the autonomic nervous system. Like the brain, the ENS is composed of neurons that are surrounded by glial cells. Enteric glia are a unique type of peripheral glia that are similar to astrocytes of the CNS. Yet enteric glial cells also differ from astrocytes in many important ways. The roles of enteric glial cell populations in the gut are beginning to come to light and recent evidence implicates enteric glia in almost every aspect of gastrointestinal physiology and pathophysiology. However, elucidating the exact mechanisms by which enteric glia influence gastrointestinal physiology and identifying how those roles are altered during gastrointestinal pathophysiology remain areas of intense research. The purpose of this e-book is to provide an introduction to enteric glial cells and to act as a resource for ongoing studies on this fascinating population of glia. Table of Contents: Introduction / A Historical Perspective on Enteric Glia / Enteric Glia: The Astroglia of the Gut / Molecular Composition of Enteric Glia / Development of Enteric Glia / Functional Roles of Enteric Glia / Enteric Glia and Disease Processes in the Gut / Concluding Remarks / References / Author Biography

Gap Junctions in the Nervous System

Gap Junctions in the Nervous System PDF Author: David C. Spray
Publisher: Springer Science & Business Media
ISBN: 3662219352
Category : Medical
Languages : en
Pages : 321

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Book Description
This book deals with the types of gap junction proteins (connexins) and their distribution within the nervous system, the physiological properties of channels formed of each connexin, and the role of gap junction channels in functions of normal and pathological brain and peripheral nerve. Although glial tissue is emphasized, additional groups of chapters deal with neurons in the central nervous system and with the retina.

Astrocytes and Epilepsy

Astrocytes and Epilepsy PDF Author: Jacqueline A. Hubbard
Publisher: Academic Press
ISBN: 0128026243
Category : Medical
Languages : en
Pages : 395

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Book Description
Epilepsy is a devastating group of neurological disorders characterized by periodic and unpredictable seizure activity in the brain. There is a critical need for new drugs and approaches given than at least one-third of all epilepsy patients are not made free of seizures by existing medications and become "medically refractory". Much of epilepsy research has focused on neuronal therapeutic targets, but current antiepileptic drugs often cause severe cognitive, developmental, and behavioral side effects. Recent findings indicate a critical contribution of astrocytes, star-shaped glial cells in the brain, to neuronal and network excitability and seizure activity. Furthermore, many important cellular and molecular changes occur in astrocytes in epileptic tissue in both humans and animal models of epilepsy. The goal of Astrocytes and Epilepsy is to comprehensively review exciting findings linking changes in astrocytes to functional changes responsible for epilepsy for the first time in book format. These insights into astrocyte contribution to seizure susceptibility indicate that astrocytes may represent an important new therapeutic target in the control of epilepsy. Astrocytes and Epilepsy includes background explanatory text on astrocyte morphology and physiology, epilepsy models and syndromes, and evidence from both human tissue studies and animal models linking functional changes in astrocytes to epilepsy. Beautifully labelled diagrams are presented and relevant figures from the literature are reproduced to elucidate key findings and concepts in this rapidly emerging field. Astrocytes and Epilepsy is written for neuroscientists, epilepsy researchers, astrocyte investigators as well as neurologists and other specialists caring for patients with epilepsy. - Presents the first comprehensive book to synthesize historical and recent research on astrocytes and epilepsy into one coherent volume - Provides a great resource on the field of astrocyte biology and astrocyte-neuron interactions - Details potential therapeutic targets, including chapters on gap junctions, water and potassium channels, glutamate and adenosine metabolism, and inflammation

The Endothelium

The Endothelium PDF Author: Michel Félétou
Publisher: Morgan & Claypool Publishers
ISBN: 1615041230
Category : Science
Languages : en
Pages : 309

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Book Description
The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References

P2 Purinoceptors

P2 Purinoceptors PDF Author: Derek Chadwick
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 360

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Book Description
Many different pathological conditions are currently under investigation as therapeutic targets of purines including cancer, cardiovascular conditions, behavioural disorders, inflammation, immunoregulation, and neuroendocrine function. This book draws together research on all aspects of P2 purinoceptors and discusses their use in different therapeutic areas.

From Molecules to Networks

From Molecules to Networks PDF Author: Ruth Heidelberger
Publisher: Academic Press
ISBN: 0080920837
Category : Psychology
Languages : en
Pages : 654

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Book Description
An understanding of the nervous system at virtually any level of analysis requires an understanding of its basic building block, the neuron. From Molecules to Networks provides the solid foundation of the morphologic, biochemical, and biophysical properties of nerve cells. All chapters have been thoroughly revised for this second edition to reflect the significant advances of the past 5 years. The new edition expands on the network aspects of cellular neurobiology by adding a new chapter, Information Processing in Neural Networks, and on the relation of cell biological processes to various neurological diseases. The new concluding chapter illustrates how the great strides in understanding the biochemical and biophysical properties of nerve cells have led to fundamental insights into important aspects of neurodegenerative disease. - Written and edited by leading experts in the field, the second edition completely and comprehensively updates all chapters of this unique textbook - Discusses emerging new understanding of non-classical molecules that affect neuronal signaling - Full colour, professional graphics throughout - Includes two new chapters: Information Processing in Neural Networks - describes the principles of operation of neural networks and the key circuit motifs that are common to many networks in the nervous system. Molecular and Cellular Mechanisms of Neurodegenerative Disease - introduces the progress made in the last 20 years in elucidating the cellular and molecular mechanisms underlying brain disorders, including Amyotrophic Lateral Sclerosis (ALS), Parkinson disease, and Alzheimer's disease