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The importance of chloride ions in cell physiology has not been fully recognized until recently, in spite of the fact that chloride (Cl-), together with bicarbonate, is the most abundant free anion in animal cells, and performs or determines fundamental biological functions in all tissues. For many years it was thought that Cl- was distributed in thermodynamic equilibrium across the plasma membrane of most cells. Research carried out during the last couple of decades has led to a dramatic change in this simplistic view. We now know that most animal cells, neurons included, exhibit a non-equilibrium distribution of Cl- across their plasma membranes. Over the last 10 to 15 years, with the growth of molecular biology and the advent of new optical methods, an enormous amount of exciting new information has become available on the molecular structure and function of Cl- channels and carriers. In nerve cells, Cl- channels and carriers play key functional roles in GABA- and glycine-mediated synaptic inhibition, neuronal growth and development, extracellular potassium scavenging, sensory-transduction, neurotransmitter uptake and cell volume control. Disruption of Cl- homeostasis in neurons underlies pathological conditions such as epilepsy, deafness, imbalance, brain edema and ischemia, pain and neurogenic inflammation. This book is about how chloride ions are regulated and how they cross the plasma membrane of neurons. It spans from molecular structure and function of carriers and channels involved in Cl- transport to their role in various diseases. The first comprehensive book on the structure, molecular biology, cell physiology, and role in diseases of chloride transporters / channels in the nervous system in almost 20 years Chloride is the most abundant free anion in animal cells. THis book summarizes and integrates for the first time the important research of the past two decades that has shown that Cl- channels and carriers play key functional roles in GABA- and glycine-mediated synaptic inhibition, neuronal growth and development, extracellular potassium scavenging, sensory-transduction, neurotransmitter uptake and cell volume control The first book that systematically discusses the result of disruption of Cl- homeostasis in neurons which underlies pathological conditions such as epilepsy, deafness, imbalance, brain edema and ischemia, pain and neurogenic inflammation Spanning topics from molecular structure and function of carriers and channels involved in Cl- transport to their role in various diseases Involves all of the leading researchers in the field Includes an extensive introductory section that covers basic thermodynamic and kinetics aspects of Cl- transport, as well as current methods for studying Cl- regulation, spanning from fluorescent dyes in single cells to knock-out models to make the book available for a growing population of graduate students and postdocs entering the field
This is a book about how Cl- crosses the cell membranes of nerve, muscle, and glial cells. Not so very many years ago, a pamphlet rather than book might have resulted from such an endeavor! One might ask why Cl-, the most abundant biological anion, attracted so little attention from investigators. The main reason was that the prevailing paradigm for cellular ion homeostasis in the 1950s and 1960s assigned Cl- a ther modynamically passive and unspecialized role. This view was particularly prominent among muscle and neuroscience investigators. In searching for reasons for such a negative (no pun intended) viewpoint, it seems to us that it stemmed from two key experimental observations. First, work on frog skeletal muscle showed that Cl- was passively distributed between the cytoplasm and the extracellular fluid. Second, work on Cl- transport in red blood cells confirmed that the Cl- transmembrane distribution was thermodynamically passive and, in addition, showed that Cl- crossed the mem brane extremely rapidly. This latter finding [for a long time interpreted as being the result of a high passive chloride electrical permeability(? CI)] made it quite likely that Cl- would remain at thermodynamic equilibrium. These two observations were gener alized and virtually all cells were thought to have a very high P Cl and a ther modynamically passive Cl- transmembrane distribution. These concepts can still be found in some physiology and neuroscience textbooks.
Single membrane channels are created through combination of two distinct membrane protein families, pannexins and connexins. These channels function as aqueous pores absorbent to small molecules and ions, to permit the diffusional interchange between the intracellular and extracellular environments. Ion fluxes across the plasma membrane in all mammalian cells are controlled by these specific membrane proteins. The channels create functional oligomeric complexes by interacting with ancillary proteins that contribute to health maintenance and cellular homeostasis. Membrane channels having varied ion selectivity modulate membrane excitability and potential. The formation of action potential triggers muscle contraction, among other cellular functions. These proteins are targets of many drugs ranging from antiepileptics to analgesics because of their role in the pathophysiology of numerous human diseases. Thus, ion channel dysfunction causes the onset of a variety of human diseases known as channelopathies, such as metabolic, cardiovascular, neural and autoimmune diseases. This book aims to shed light on the physiology and pathology of channels in the nervous system. It presents researches and studies performed by experts across the globe. This book will serve as a reference to a broad spectrum of readers.
Cell Physiology Source Book gathers together a broad range of ideas and topics that define the field. It provides clear, concise, and comprehensive coverage of all aspects of cellular physiology from fundamental concepts to more advanced topics. The 4e contains substantial new material. Most chapters have been thoroughly reworked. The book includes chapters on important topics such as sensory transduction, the physiology of protozoa and bacteria, and synaptic transmission. Authored by leading researchers in the field Clear, concise, and comprehensive coverage of all aspects of cellular physiology, from fundamental concepts to more advanced topics Full color illustrations
Cell Physiology Source Book gathers together a broad range of ideas and topics that define the field. It provides clear, concise, and comprehensive coverage of all aspects of cellular physiology from fundamental concepts to more advanced topics. The 4e contains substantial new material. Most chapters have been thoroughly reworked. The book includes chapters on important topics such as sensory transduction, the physiology of protozoa and bacteria, and synaptic transmission. Authored by leading researchers in the field Clear, concise, and comprehensive coverage of all aspects of cellular physiology, from fundamental concepts to more advanced topics Full color illustrations
This book sheds new light on the physiology, molecular biology and pathophysiology of epithelial ion channels and transporters. It combines the basic cellular models and functions by means of a compelling clinical perspective, addressing aspects from the laboratory bench to the bedside. The individual chapters, written by leading scientists and clinicians, explore specific ion channels and transporters located in the epithelial tissues of the kidney, intestine, pancreas and respiratory tract, all of which play a crucial part in maintaining homeostasis. Further topics include the fundamentals of epithelial transport; mathematical modeling of ion transport; cell volume regulation; membrane protein folding and trafficking; transepithelial transport functions; and lastly, a discussion of transport proteins as potential pharmacological targets with a focus on the pharmacology of potassium channels.
This book discusses unique ion channels and transporters that are located within epithelial tissues of various organs including the kidney, intestine, pancreas and respiratory tract. The authors will show, that each of these channels and transporters play crucial roles in transepithelial ion and fluid transport across epithelia and their responsibility in maintaining homeostasis. The reader gains an understanding of the fundamentals of epithelial ion transport, in terms of function, modelling, regulation, trafficking, structure and pharmacology. This is the third of three volumes highlighting the importance of epithelial ion channels and transporters in basic physiology and pathophysiology of human diseases. The focus of this volume lies with different ion channel and transporter families. Additionally, this volume benefits from pharmaceutical contributors and their insights into recent pre-clinical drug discovery efforts and results from clinical trials. Overall, these chapters offer a more thorough coverage of individual epithelial ion channels and transporters from the 1st Edition, along with eleven new chapters. That makes Volume 3 an insightful contribution for physiology students, scientists and clinicians.
The book covers the functional significance and properties of erythrocytes, their generation, senescence, and suicidal death. It further summarizes knowledge about hormones influencing erythrocyte formation including erythropoietin as well as disorders affecting and involving erythrocytes such as anemia, malaria, and sepsis.This seminal work forms a unique reference on the most abundant cell type in mammals and will be an invaluable resource for students in the life sciences./a
Membrane Transporters in the Pathogenesis of Cardiovascular and Lung Disorders, Volume 83, the latest release in the Current Topics in Membranes series, highlights new advances in the field, with this volume presenting chapters from recognized experts on topics such as cardiotonic steroids, Na+, K+ pumps and vascular fibrosis, purinergic signaling in the lung, structural models of a2-subunit N-termini and binding interfaces, ubiquitous and cell type-specific transcriptomic changes triggered by dissipation of monovalent cation gradients, the Na, K-ATPase alpha2 isoform in cardiovascular pathologies, the role of cell swelling and volume-sensitive ion channels in stroke pathology, structure-function relationships in the renal NaCl cotransporter, and more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Current Topics in Membranes series Includes the latest information on membrane ion transporters
In the past several years, there has been an exciting body of new research that links impairments in the expression or function of neuronal chloride transporters to a growing number of diseases spanning from autism to brain aging. This book introduces the core concepts and highlights the recent advances in understanding the physiology and pathophysiology of the KCC and NKCC families of neuronal chloride transporters. Neuronal chloride transporter biology is reviewed, including roles in setting the transmembrane chloride gradient and the chloride transport-independent functions, such as regulating excitatory neurotransmission. Chapters are also dedicated to addressing the structure, post-translational modification, membrane trafficking, and protein interaction partners of neuronal chloride transporters, as well as the genetic and environmental factors that regulate their expression in neurons and the novel therapeutic approaches that target neuronal chloride transporters to treat neurological diseases. This new volume will provide readers with an up-to-date summary of the recent advances in neuronal chloride transporter research, with particular emphasis on some of the key emerging topics in the field. Summarizes roles of KCCs and NKCCs in regulating inhibitory and excitatory neurotransmission Reviews the molecular and cellular biology of neuronal chloride transporters Links neuronal chloride transporter deficiencies to autism, epilepsy, depression, and more Identifies role of transporter deficiencies in pain as well as brain and spinal cord injury Discusses drug research targeting neuronal chloride transporters for nervous system diseases