Gap Junction-Mediated Intercellular Signalling in Health and Disease


Book Description

Gap junctions are key elements in communication between cells in multicellular organisms. It is clear that their activity is essential for normal embryonic development and normal function in adult organs, although the individual roles of the proteins that form the channels (connexins) are not yet fully understood. The last few years have seen considerable progress in this field and exciting new issues concerning gap junctional intercellular communication are being raised. Perturbed gap junction activity is beginning to be linked to certain pathologies, e.g. mutations in the major connexin of the heart have been found in human patients suffering from visceroatrial heterotaxia syndrome and mutations in the gene encoding another connexin have been found in patients with Charcot-Marie-Tooth disease. This book is the first to highlight the recent progress in understanding gap junction structure and to discuss the specific roles of individual connexins. It features contributions from an interdisciplinary group of experts who review the role of gap junctions in the heart, the retina and lens, the auditory system, the reproductive system, and in cell proliferation and cancer. The book will appeal to people interested in cell and molecular biology, embryonic development, neurobiology, cardiology, gynaecology and oncology.




Gap Junctions in the Nervous System


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.




Intercellular Communication in Cancer


Book Description

Cells are by nature compelled to live in groups. They develop dependence over signaling cues received from their microenvironment, in particular from other cells, whether of their own “kind” or of a different type. Therefore, communicating with these cells is a critical aspect of their behavior and fate, as they live and die normally or as they undergo disease-related pathological changes, with dramatic repercussions. In this book, we have asked expert researchers in the field of Intercellular Communication in Cancer to provide chapters on different aspects of interaction between neighboring cells, in the context of cancer diseases. We have specifically focused our efforts on membrane-to-membrane contact-based rather than growth factors-mediated modes of intercellular communications. The contributing authors provide an extensive overview of their respective area of specialization, with an in-depth discussion of the molecular mechanisms of cell-cell interactions, the impact on tumor progression and response to therapies, as well as the cancer diagnostic value of this scientific information. This book aims to introduce essential aspects of the normal and pathological cellular fate and homeostasis to both scientists and clinicians, and also to provide established researchers with an update on the novelties and future directions this expanding field is witnessing.




Gap Junctions in the Brain


Book Description

Gap junctions between glial cells or neurons are ubiquitously expressed in the mammalian brain and play a role in brain development including cell differentiation, cell migration and survival, and tissue homeostasis, as well as in human diseases including hearing loss, neuropathies, epilepsy, brain trauma, and cardiovascular disease. This volume provides neuroscience researchers and students with a single source for information covering the physiological, behavioral and pathophysiological roles of gap junctions in the brain. In addition, the book also discusses human disease conditions associated with mutations in single gap junction connexion genes, making it applicable to clinicians doing translational research. Finally, it includes reviews of pharmacological studies with gap junction blockers and openers, summarizing information obtained from phenotyping gap junctions mouse mutants. - Serves as the most current and comprehensive reference available covering the physiological, behavioral and pathophysiological roles of gap junctions in the brain - Chapters summarize knowledge of the basic physiology of gap junctions in the brain, as well as of human disease conditions associated with mutations in single gap junction connexin genes - Includes reviews of pharmacological studies with gap junction blockers and openers, summarizing information obtained from phenotyping gap junctions mouse mutants




Gap Junction Channels and Hemichannels


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.




The Endothelium


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




Intercellular Communication through Gap Junctions


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.




Astrocytes and Epilepsy


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




Colonic Motility


Book Description

Three distinct types of contractions perform colonic motility functions. Rhythmic phasic contractions (RPCs) cause slow net distal propulsion with extensive mixing/turning over. Infrequently occurring giant migrating contractions (GMCs) produce mass movements. Tonic contractions aid RPCs in their motor function. The spatiotemporal patterns of these contractions differ markedly. The amplitude and distance of propagation of a GMC are several-fold larger than those of an RPC. The enteric neurons and smooth muscle cells are the core regulators of all three types of contractions. The regulation of contractions by these mechanisms is modifiable by extrinsic factors: CNS, autonomic neurons, hormones, inflammatory mediators, and stress mediators. Only the GMCs produce descending inhibition, which accommodates the large bolus being propelled without increasing muscle tone. The strong compression of the colon wall generates afferent signals that are below nociceptive threshold in healthy subjects. However, these signals become nociceptive; if the amplitudes of GMCs increase, afferent nerves become hypersensitive, or descending inhibition is impaired. The GMCs also provide the force for rapid propulsion of feces and descending inhibition to relax the internal anal sphincter during defecation. The dysregulation of GMCs is a major factor in colonic motility disorders: irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and diverticular disease (DD). Frequent mass movements by GMCs cause diarrhea in diarrhea predominant IBS, IBD, and DD, while a decrease in the frequency of GMCs causes constipation. The GMCs generate the afferent signals for intermittent short-lived episodes of abdominal cramping in these disorders. Epigenetic dysregulation due to adverse events in early life is one of the major factors in generating the symptoms of IBS in adulthood.