Molecular Biology Of Membrane Transport Disorders

When the six of us gathered to start planning for what was to be the Third Edition of Physiology of Membrane Disorders, it was clear that since 1986, when the Second Edition appeared, the field had experienced the dawning of a new era dominated by a change in focus from phenomenology to underlying mechanisms propelled by the power of molecular biology. In 1985, detailed molecular information was available for only three membrane transporters: the lac permease, bacterial rhodopsin, and the acetylcholine receptor. During the decade that has since elapsed, almost all of the major ion channels and transport proteins have been cloned, sequenced, mutagenized, and expressed in homologous as well as heterologous cells. Few, if any, of the transporters that were identified during the previous era have escaped the probings of the new molecular technologies and, in many instances, considerable insight has been gained into their mechanisms of function in health and disease. Indeed, in some instances novel, unexpected transporters have emerged that have yet to have their functions identified. The decision to adopt the new title Molecular Biology of Membrane Transport Disorders was a natural outgrowth of these considerations.

Studies of membrane transporters have had great impact on our und- standing human diseases and the design of effective drugs. About 30% of current clinically marketed drugs are targeting membrane transporters or channels. Membrane Transporters: Methods and Protocols provides various practical methodologies for the ongoing research on membrane transporters. To provide readers the most up-to-date information, several emerging fields and methodologies are embraced in this book, including pharmacogenomics, bioin-formatics, and microarray technology. Pharmacogenomics studies of membrane transporters are useful in drug discovery and in predicting drug responses in the clinic. In this volume, the current status of pharma- genomics studies of transporters is reviewed and research methodologies in this field are described. Transporter classification is important in studying the structure and function of membrane transporters and has thus triggered intensive interest in recent years. Membrane Transporters: Methods and Protocols provides a systematic classification of all transmembrane transport proteins found in living org- isms on Earth. This classification system will be helpful for further studies on various aspects of membrane transporters, especially for such large-scale gene expression studies as those employing microarray technologies. Bioinformatics is frequently used in transporter studies and has become indispensable for all kinds of research methods. Commonly used bio- formatics methods, such as databases and tools for sequence analysis and - tif studies, are explained in order to facilitate membrane transporters research. Because of heterogeneous sources and tremendous amounts of data, data in- gration has become one of the most important issues in transporter studies.

51 worldwide leading experts in the field of erythrocyte research contributed to this first book on transport processes in red blood cells. It explains the latest findings on the basis of well-established principles, in an accessibly structured and carefully organized compilation.

The second edition of Physiology of Membrane Disorders represents an extensive revision and a considerable expansion of the first edition . Yet the purpose ofthe second edition is identical to that of its predecessor, namely, to provide a rational analysis of membrane transport processes in individual membranes, cells, tissues, and organs, which in tum serves as a frame of reference for rationalizing disorders in which derangements of membrane transport processes playa cardinal role in the clinical expression of disease. As in the first edition, this book is divided into a number of individual, but closely related, sections. Part V represents a new section where the problem of transport across epithelia is treated in some detail. Finally, Part VI, which analyzes clinical derangements, has been enlarged appreciably. THE EDITORS xi Preface to the First Edition The purpose of this book is to provide the reader with a rational frame of reference for assessing the pa thophysiology of those disorders in which derangements of membrane transport processes are a major factor responsible for the clinical manifestations of disease. In the present context, we use the term "membrane transport to refer to those molecular processes whose cardinal function, broadly speaking, is processes" in a catholic sense, the vectorial transfer of molecules-either individually or as ensembles-across biological interfaces, the latter including those interfaces which separate different intracellular compartments, the cellular and extracellular com partments, and secreted fluids-such as glomerular filtrate-and extracellular fluids.

The burgeoning interest in biomembranes in recent years has been such that "membranology" is now virtuMtyasubject in its own right, cutting vertically, as it were, through the strata of conventional disciplines from mathematics and physics, through chemistry, to biology. The very scope of the topic is thus so daunting that it is tempting to treat it only at one stratum of this hierarchy, be it the biophysics of phospholipid bilayers or the biochemistry of interactions at the cell surface. Such an approach is entirely valid, particularly among specialists with common interests. However, this approach does present a distorted perspective to the newcomer to the field, and, more significantly, it fails to stimulate cross fertil ization of ideas among workers at the various disciplinary levels. For example, as in all areas of molecular biology, the clinicians are frequently unaware of the contributions to their problems that might be made by the application of more basic knowledge and techniques. Conversely, biochemists or biophysicists may be ignorant of the existing practical problems to which they might address their expertise.

This text attempts to introduce the molecular biology of cell membranes to students and professionals of diverse backgrounds. Although several membrane biology books are available, they do not integrate recent knowledge gained using modern molecular tools with more traditional membrane topics. Molecular techniques, such as cDNA cloning and x-ray diffraction, have provided fresh insights into cell membrane structure and function. The great excitement today, which I attempt to convey in this book, is that molecular details are beginning to merge with physiological responses. In other words, we are beginning to understand precisely how membranes work. This textbook is appropriate for upper-level undergraduate or beginning graduate students. Readers should have previous or concurrent coursework in biochemistry; prior studies in elementary physiology would be helpful. I have found that the presentation of topics in this book is appropriate for students of biology, biochemistry, biophysics and physiology, chemistry, and medicine. This book will be useful in courses focusing on membranes and as a supplementary text in biochemistry courses. Professionals will also find this to be a useful resource book for their personal libraries.

This book elucidates the mechanisms involved in biological membrane functions. It describes the new modalities and characterization for basic in vitro as well as computer models of biological membranes. Biological membranes are analyzed in terms of advances in molecular dynamics. The individual chapters provide an in depth analysis of images from various biological models. The potential of membrane models in the context of treatment trials is discussed. The authors present new insights and current concepts for treatment procedures (nanocarriers, electroporation, channel blockers).