Epithelial Anion Transport in Health and Disease


Book Description

Cl- absorption and HCO3- secretion are intimately associated processes vital to epithelial function, itself a key physiological activity. Until recently the transporters responsible remained obscure, but a breakthrough occurred with the discovery of the SLC26 transporters family. It is now clear that the SLC26 transporters have broad physiological functions since mutations in several members are linked to a variety of diseases. This book describes the properties of this family in detail, with contributions from the leading global researchers in the field. Complementary views from experts on other ion channels are offered in the discussions, which make fascinating reading. This family consists of at least 10 genes, each of which has several splice variants. Most members of the family are expressed in the luminal membrane of epithelial cells. Characterization of anion transport by three members has revealed that all function as Cl-/HCO3- exchangers, suggesting that SLC26 transporters are responsible for the luminal Cl-/HCO3- exchange activity. The SLC26 transporters are activated by the CF transmembrane conductance regulator and activate it in turn, leading to a model in which these molecules act together to mediate epithelial Cl- absorption and HCO3- secretion. The book includes chapters on the transport of other molecules by the SLC26 family, including oxalate in the kidney and sugars in cochlear hair cells amongst others. It also describes recent discoveries that most SLC26 transporters bind to scaffold proteins and that they all contain a conserved domain predicted to participate in protein-protein interactions. These suggest the SLC26 transporters exist in complexes with other Cl- and HCO3- transporters, and possibly other regulatory proteins. This book explores the functional role of these interactions, leading to better understanding of transepithelial fluid and electrolyte secretion and the diseases associated with it.




Ion Channels and Transporters of Epithelia in Health and Disease


Book Description

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.




Basic Epithelial Ion Transport Principles and Function


Book Description

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. As the authors show, these channels and transporters play crucial roles in transepithelial ion and fluid transport across epithelia and their contribution to maintaining homeostasis. Readers will be introduced to the fundamentals of ion transport in terms of function, modelling, regulation, structure and pharmacology. This is the first of three volumes highlighting the importance of epithelial ion channels and transporters in basic physiology and pathophysiology of human diseases. This volume focuses on basic fundamentals of epithelial transport physiology. There is a range of chapters dedicated to specific aspects of epithelial ion transport and cell function. Accordingly, the authors discuss techniques used to determine epithelial function, principles of epithelia transport, polarization of epithelial cells, mathematical modelling of epithelial ion transport, protein folding of ion channels, degradation epithelial ion channels, fundamentals of epithelial sodium, potassium and chloride transport, fundamentals of bicarbonate secretion, volume regulation, and microRNA regulation of epithelial channels and transporters. Given its scope, Volume 1 offers a valuable resource for physiology students, scientists and clinicians alike.




Studies of Epithelial Transporters and Ion Channels


Book Description

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.




Ion Transport Across Epithelial Tissues and Disease


Book Description

This book discusses the unique ion channels and transporters found within the epithelial tissues of various organs, including the kidney, intestine, pancreas and respiratory tract. Authors focus on demonstrating the crucial roles that each of these channels and transporters play in transepithelial ion and fluid transport across epithelia, as well as in maintaining homeostasis. It allows readers to gain an understanding of the fundamentals of ion transport, in terms of function, modelling, regulation, trafficking, structure and pharmacology. This is the second of three volumes highlighting the importance of epithelial ion channels and transporters in basic physiology and pathophysiology of human diseases. This volume focuses on a wide array of epithelial tissues and the use of organoids to study epithelial function. Furthermore, clinical researchers and basic scientists from various fields provide a medical perspective on the physiology of a number of tissues and organs of the body including the pancreas, intestine, sweat glands, mammary gland, inner ear epithelia, retinal pigment epithelia of the eye, choroid plexus, and the ectodermal epithelia in dental enamel formation. This volume aims to ‘round out’ the reader’s journey from basic science to the laboratory bench and clinical management of molecular diseases, making Volume 2 a must-read for students and scientists in the field of physiology, as well as for clinicians.







Intestinal Water and Electrolyte Transport in Health and Disease


Book Description

The unique architecture and physiology of the mammalian intestine, together with a tightly coordinated regulatory system, allows for the handling and absorption of as much as 9 L of fluid a day with 98% or greater efficiency. Advances in the past 40 years have made inroads into revealing the intricacies and interplay of numerous ion transporters and their modulators that are responsible for intestinal electrolyte and water transport. Studies of two devastating diseases, the virulent infectious disease cholera and the autosomal recessive disease cystic fibrosis, were largely responsible for this information explosion. These advances have been critical in the development of new therapeutic strategies to combat life-threatening diseases of varying etiologies ranging from enteric infections to cystic fibrosis and inflammatory bowel diseases. Yet, the story is far from complete, and progress needs to continue on translating information gained from reductionistic cell and tissue culture models, in vivo models, and ultimately human studies and on improving therapeutic approaches. This book reviews the current status of our knowledge of fluid transport across the intestine, including the complexities of transcellular and paracellular ion transport down the length of the intestine and how aberrations of normal physiological processes lead to disease. Table of Contents: Overview / Epithelial Cell and Tissue Architecture / Principles of Transepithelial Electrolyte and Water Movement / Intestinal Architecture and Electrolyte Transport / Electrolyte Transporters--Pumps, Carriers, and Channels / Water Transport / Regulation / Intestinal Disorders and Advances Toward Better Treatment of Intestinal Disorders / Conclusion / References







The Role of Pendrin in Health and Disease


Book Description

This book reviews the current state of knowledge on the genetics, molecular biology and physiology of pendrin, with a particular focus on pendrin dysfunction and the consequences for human health. Pendrin is a membrane transport protein expressed in the thyroid, inner ear, kidney and airways, and was recently found in a variety of other tissues and organs. Pendrin malfunction may cause a genetic disease called Pendred syndrome or non-syndromic deafness. The book provides a thorough description of the multifaceted role of pendrin in human health and disease. As such, it offers an invaluable tool for physiology and pathology researchers, while also providing essential guidance for otorhinolaryngologists and endocrinologists in the diagnosis of Pendred syndrome and pendrin-related deafness.




The Pathophysiology of Biliary Epithelia


Book Description

This book is a comprehensive review of the biliary epithelia pathophysiology. Biliary epithelial cells (also referred to as cholangiocytes) line the intra- and extrahepatic bile ducts. Cholangiocytes have immerged in the last several years as one of the more important epithelial cells in the gastrointestinal system due to their large contribution to bile formation and tendency to be involved in human diseases. The book’s 35 chapters represent a nearly complete review of the function and disease of bile ducts. The gestational development of bile ducts is shown to be a complex interaction between hepatocyte and biliary precursors. The structure of bile ducts can be defined by ultrastructural studies and by 3D reconstruction studies which show that the bile duct system resembles a tree. The array of membrane transporters and channels involved in ductal absorption and secretion of water and electrolytes is reviewed. Like other gastrointestinal epithelial cells, the physiologic responses of cholangiocytes are regulated by hormones, nerve input, cytokines, factors in bile and intracellular signals (e.g., cyclic AMP and intracellular calcium). The potential role of the cholangiocyte in production of collagen in cholestatic liver disease is discussed. A number of important models used in the study of cholangiocyte physiology and reactions to injury are reviewed. Finally the relationships between the cholangiocyte responses and human liver diseases are discussed. While many basic scientists and hepatologists who devote their careers to the study of the liver will find this book useful, the intended audience of this book is the more heterogeneous group of individuals who study clinical and/ or basic science digestive physiology and due to their interest in epithelial function will find the cutting edge information in this book both enlightening and useful to their progression of their work.