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Ion channels are membrane proteins that selectively allow ions to flow down their electrochemical gradient across the cellular membrane. They localize in both plasma and intracellular membranes and regulate a variety of functions such as neuronal excitability, heartbeat, muscle contraction and hormones release. Thus, understanding the molecular mechanism of ion channels function and regulation is one of the key goals of modern Biophysics. During my PhD thesis, by combining patch-clamp measurements with site-direct mutagenesis, fluorophore labeling experiments and pharmacological assays, I explored some functional and structural properties of different ion transporters: the Na+/Ca2+ exchanger (NCX); the large conductance Ca2+-voltage activated K+ channel (BK) channel; the human Transient receptor potential, member A1 (TRPA1) channel.

Ion channels. --- Patch-clamp techniques (Electrophysiology)

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In recent years, the ryanodine receptor has emerged as a new and very promising target for the treatment of several cardiovascular disorders, including cardiac arrhythmias and heart failure. This volume is the most current publication devoted to the major intracellular calcium-release channel, the ryanodine receptor. "In this series of brief but informative chapters, the contributions progress from the basic gene family and primary structure, through its 3D structure so far, to its regulation and physiology." David E. Clapham, MD, PhD Professor of Neurobiology and Pediatrics Harvard Medical School Dr. Xander H.T. Wehrens received his M.D. and Ph.D. degrees from Maastricht University in the Netherlands. His research has mainly concentrated on molecular mechanisms of cardiac arrhythmias, in particular in the setting of inherited arrhythmogenic syndromes and congestive heart failure. This work has led to the development of novel anti-arrhythmic therapies. He is currently a research scientist in the Department of Physiology and Cellular Biophysics at the College of Physicians and Surgeons of Columbia University. Dr. Andrew R. Marks is the Chair and Professor of the Department of Physiology and Cellular Biophysics at Columbia University College of Physicians and Surgeons. Dr. Marks' research has focused on understanding how macromolecular signaling complexes regulate ion channel function in muscle and non-muscle systems, and on the regulation of vascular smooth muscle proliferation and migration. His work has contributed new understandings of fundamental mechanisms that regulate muscle contraction that have lead to the discovery of molecular defects that contribute to heart failure and fatal cardiac arrhythmias.

Ryanodine --- Calcium channels. --- Receptors. --- Channels, Calcium --- Ion channels --- Calcium release channels --- Calcium-ryanodine receptor complex --- Calcium channels --- Cardiology. --- Heart --- Internal medicine --- Diseases

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oltage-gated calcium channels are essential mediators of a range of physiological functions, including the communication between nerve Vcells, the regulation of heart beat, muscle contraction, and secretion of hormones such as insulin. Consequently, these channels are critical phar­ macological targets in the treatment of a variety of disorders, such as epi­ lepsy, hypertension, and pain. Voltage-gated calcium channels have there­ fore been subject to intense study by numerous investigators over the past few decades, and an immense body of work has accumulated. In this book, we provide the first comprehensive overview of our current state of knowl­ edge concerning this exciting field of research. Leading off with a general review of calcium signaling and techniques to measure calcium channel ac­ tivity, the book delves into a provocative overview of the history of the cal­ cium channel field, contributed by one of the key pioneers in the field. Dr. Richard Tsien. This is followed by an in depth review of the biochemical and molecular biological characterization of calcium channel genes by Drs. Catterall and Snutch whose research has resulted in major advances in the calcium channel field. A number of chapters are dedicated towards various aspects of calcium channel structure and function, including channel gat­ ing, permeation, modulation and interactions with members of the exo- totic machinery—contributed by both established leaders and rising stars in the field.

Calcium channels. --- Ion channels. --- Channels, Ion --- Biological transport, Active --- Ion-permeable membranes --- Membrane proteins --- Channels, Calcium --- Ion channels --- Cytology. --- Life sciences. --- Neurosciences. --- Human physiology. --- Toxicology. --- Cell Biology. --- Life Sciences, general. --- Biological and Medical Physics, Biophysics. --- Human Physiology. --- Pharmacology/Toxicology. --- Chemicals --- Medicine --- Pharmacology --- Poisoning --- Poisons --- Human biology --- Medical sciences --- Physiology --- Human body --- Neural sciences --- Neurological sciences --- Neuroscience --- Nervous system --- Biosciences --- Sciences, Life --- Science --- Cell biology --- Cellular biology --- Biology --- Cells --- Cytologists --- Toxicology --- Cell biology. --- Biophysics. --- Biological physics. --- Pharmacology. --- Drug effects --- Medical pharmacology --- Chemotherapy --- Drugs --- Pharmacy --- Biological physics --- Physics --- Physiological effect

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Sodium channels confer excitability on neurons in nociceptive pathways and exhibit neuronal tissue specific and injury regulated expression. This volume provides recent insights into the control of expression, functioning and membrane trafficking of nervous system sodium channels and reviews why sodium channel sub-types are potentially important drug targets in the treatment of pain. The roles of sodium channels in dental and visceral pain are also addressed. The emerging role of sodium channel Nav1.3 in neuropathic states is another important theme. Authors from the pharmaceutical industry discuss pharmacological approaches to the drug targeting of sodium channels, and in particular Nav1.8, exclusively expressed in nociceptive neurons. The final chapter highlights the functional diversity of sodium channels in part provided by post-transcriptional processing and the insights into sodium channel function that are being provided by tissue specific and inducible gene knock-out technology.

Pain. --- Sodium channels. --- Analgesics. --- Analgetics --- Anodynes --- Pain-killing drugs --- Pain relievers --- Painkillers --- Central nervous system depressants --- Channels, Sodium --- Ion channels --- Sodium --- Aches --- Emotions --- Pleasure --- Senses and sensation --- Symptoms --- Analgesia --- Suffering --- Physiological transport --- Neuropathology --- Pain Medicine. --- Neurosciences. --- Toxicology. --- Cytology. --- Pharmacology/Toxicology. --- Cell Biology. --- Cell biology --- Cellular biology --- Biology --- Cells --- Cytologists --- Chemicals --- Medicine --- Pharmacology --- Poisoning --- Poisons --- Neural sciences --- Neurological sciences --- Neuroscience --- Medical sciences --- Nervous system --- Toxicology --- Algiatry --- Pain medicine. --- Pharmacology. --- Cell biology. --- Drug effects --- Medical pharmacology --- Chemotherapy --- Drugs --- Pharmacy --- Physiological effect

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Ion channels play a vital role in basic physiological functions such as generation of electrical activity in nerves and muscle, control of cardiac excitability, intracellular signaling, hormone secretion, cell proliferation and many other biological processes. Because of their prevalence and the critical role they play in virtually all tissue types and organs, ion channels are also involved in a number of pathophysiological conditions. The aim of this volume is to review recent advances in the field of ion channel related diseases. Following an overview chapter summarizing the current state of ion channel screening technologies, five topics covering areas such as cancer, cardiac arrhythmias, cystic fibrosis, and pain have been selected, and the current state of knowledge is presented by leading experts in their field. Each chapter is structured to cover the biological rationale for the target, the current status in the development of agents to treat the disease, and future prospects and challenges facing each therapeutic area. The reader will receive a critical overview covering the progress made in the rapidly developing and complex field of ion channels and diseases.

Ion channels. --- Channels, Ion --- Biological transport, Active --- Ion-permeable membranes --- Membrane proteins --- Biochemistry. --- Toxicology. --- Chemistry, Organic. --- Medicine. --- Medicinal Chemistry. --- Pharmacology/Toxicology. --- Organic Chemistry. --- Molecular Medicine. --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Biology --- Chemistry --- Medical sciences --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Pathology --- Physicians --- Organic chemistry --- Chemicals --- Medicine --- Pharmacology --- Poisoning --- Poisons --- Composition --- Toxicology --- Health Workforce --- Medicinal chemistry. --- Pharmacology. --- Organic chemistry. --- Molecular biology. --- Molecular biochemistry --- Molecular biophysics --- Biochemistry --- Biophysics --- Biomolecules --- Systems biology --- Drug effects --- Medical pharmacology --- Chemotherapy --- Drugs --- Pharmacy --- Chemistry, Medical and pharmaceutical --- Chemistry, Pharmaceutical --- Drug chemistry --- Medical chemistry --- Medicinal chemistry --- Pharmacochemistry --- Physiological effect