The aim of this volume is to summarize novel findings on the function, pathophysiology, and regulation of voltage-gated Ca2+ channels and on novel concepts of their pharmacological modulation. Impressive insights into the role of channel function and regulation have come from Ca2+ channelopathies affecting the pore-forming as well as accessory subunits and channel-interacting proteins. Moreover, the long-sought molecular basis for key regulatory pathways have been discovered as well as exciting concepts of their subtype-selective pharmacological modulation.

This book covers the tremendous progress in the current understanding of the molecular physiology of voltage-gated calcium channels. This book includes unparalleled insights into structural features of calcium channels due to X-ray crystallography and cryo-EM, which in turn yielded critical information into how these channels function under normal and pathophysiological conditions, and how they interact with calcium channel therapeutics. The chapters investigate how, with the advent of high throughput genome sequencing, numerous mutations in various calcium channel genes have been identified in patients with neurological, cardiovascular, neuropsychiatric and other disorders. This is further complemented through a much larger in vivo toolkit such as knock-out and knock-in mice. The chapters further discuss the increased complexity of calcium channel physiology that arises from mRNA editing and splicing. Finally, the book also provides an overview of the updated research on calcium channel inhibitors that can be used both in vivo and in vitro, and which may serve as a spring board for new calcium channel therapeutics for human disease. Voltage-Gated Calcium Channels is useful for academic researchers at all levels in neuroscience, biophysics, cell biology and drug discovery.

This book discusses voltage-gated ion channels and their importance in drug discovery and development. The book includes reviews of the channel genome, the physiological bases of targeting ion channels in disease, the unique technologies developed for ion channel drug discovery, and the increasingly important role of ion channel screening in cardiac risk assessment. It provides an important reference for research scientists and drug discovery companies.

Voltage-gated calcium channels are critical regulators of cytoplasmic levels of calcium, the universal signaling ion. As such, calcium channels trigger a wide range of cellular functions, from muscle contraction to neurotransmitter secretion, and are important players in human disease. Prominent in the nervous, cardiovascular, and endocrine systems, members of the calcium channel family are targets for existing antihypertensive and anticonvulsant drugs. In addition, they are emerging targets for drugs to treat an extraordinarily diverse group of disorders, including pain, cerebral ischemia, cardiac arrhythmia, and migraine. This book reviews the compounds that target individual calcium channel subtypes and the cellular and behavioral functions governed by each different channel. It contains information for basic scientists using calcium channel antagonists as experimental tools, for behavioralists studying animal models of human disease, and for pharmaceutical scientists interested in creating the next generation of calcium channel-targeted drugs. Several factors make an entire book on calcium channel pharmacology timely.

Edited by the most prominent person in the field and top researchers at US pharmaceutical companies, this is a unique resource for drug developers and physiologists seeking a molecular-level understanding of ion channel pharmacology. After an introduction to the topic, the authors evaluate the structure and function of ion channels, as well as related drug interaction. A section on assay technologies is followed by a section each on calcium, sodium and potassium channels. Further chapters cover genetic and acquired channelopathies, before the book closes with a look at safety issues in ion channel drug development. For medicinal and pharmaceutical chemists, biochemists, molecular biologists and those working in the pharmaceutical industry.

The aim of the present book is to comprehensively review current advances in understanding of genetics, structural biology, pharmacology of potassium channels and their roles in disease as well as to identify current gaps in knowledge. The ultimate goal is to provide a scientific foundation for better understanding of modulatory mechanisms and pharmacology of potassium channels and to use this understanding to drive future drug discovery. This book will be a must-have for academic and industrial scientists interested in physiology, pharmacology, pathology and structure-functional relationships of ion channels. The book will also be helpful for lecturers and students in the college and university classrooms, as well as for anyone interested in the state-of-the art in modern cell biology, physiology and pharmacology.

The Textbook of Ion Channels is a set of three volumes that provides a wide-ranging reference source on ion channels for students, instructors and researchers. Ion channels are mem- brane proteins that control the electrical properties of neurons and cardiac cells; medi- ate the detection and response to sensory stimuli like light, sound, odor, and taste; and regulate the response to physical stimuli like temperature and pressure. In non-excitable tissues, ion channels are instrumental for the regulation of basic salt balance that is critical for homeostasis. Ion channels are located at the surface membrane of cells, giving them the unique ability to communicate with the environment, as well as the membrane of intracellular organelles, allowing them to regulate internal homeostasis. Ion channels are fundamentally important for human health and diseases, and are important targets for pharmaceuticals in mental illness, heart disease, anesthesia, pain and other clinical appli- cations. The modern methods used in their study are powerful and diverse, ranging from single ion-channel measurement techniques to models of ion channel diseases in animals, and human clinical trials for ion channel drugs. Volume III includes coverage of key ion channel regulators and their mechanisms, the role of ion channels working in concert in selected physiological systems, and examples of ion channel mutations and dysfunction in a selection of diseases. Chapters on ion channel regulation include splice variants, calcium–calmodulin regulation, regulation by G pro- teins, and lipids. A selection of ion channels in physiological systems includes ion chan- nels of the heart, ion channels in immune cells and their role in pancreatic beta cells and regulation of insulin secretion, and the role of channels in sperm and eggs. While disease mechanisms are integrated into the chapters of Volume II, Volume III offers special consid- eration of ion channels in epilepsy, cystic fibrosis and pain syndromes. All three volumes give the reader an introduction to fundamental concepts needed to understand the mechanism of ion channels, a guide to the technical aspects of ion channel research, offer a modern guide to the properties of major ion channel families, and includecoverage of key examples of regulatory, physiological, and disease roles for ion channels.