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This book brings together leading international experts to discuss recent advances in the regulation of presynaptic voltage-gated Ca2+ channels (VGCCs), key signal transducers that represent one of the most widely modulated proteins in the body. It is now commonly accepted that presence of the VGCC complex defines an excitable cell. At a basic level, VGCCs transduce membrane potential change to chemical neurotransmitter release at presynaptic terminals. However, on-going scientific research, presented here, in areas including neuroscience, electrophysiology, pharmacology, biochemistry and, increasingly, proteomics, has revealed the widespread nature of modulation of the presynaptic VGCC complex. This book reviews and discusses the following topics: The fundamental role of the VGCC pore-forming CaVa subunit, and some of their binding partners, in presynaptic function and synaptic plasticity. Modulation of presynaptic CaVa subunits by auxiliary CaVb and a2d subunits and by their major interaction partners, such as active zone scaffolding proteins, synaptic proteins, G proteins and small GTPases, which, together, contribute to the VGCC proteome. Work at the cutting edge of research, including how direct electrophysiology recordings from presynaptic terminals and introduction of synthetic CaVa peptides into presynaptic terminals has expanded our knowledge of VGCC function. Evidence emerging over the last decade demonstrating that VGCC subunits represent bona fide molecular targets for therapeutic drug discovery. This development is illustrated by the introduction of the CaV2.2 blocker ziconotide, which represents an important proof-of-concept, but is best exemplified by the emergence of gabapentinoids, which bind the VGCC auxiliary a2d subunit, as first-line treatments for chronic neuropathic pain. Throughout, chapters are accompanied with illustrative Tables and Figure providing a useful and comprehensive summary of the current state-of-play in this area of significant therapeutic interest. Work described here also provides a solid basis for future research in this important area.

Calcium -- Physiological effect. --- Calcium channels. --- Calcium. --- Presynaptic receptors. --- Ion Channels --- Electrophysiological Processes --- Nervous System Physiological Processes --- Intercellular Junctions --- Axons --- Signal Transduction --- Nervous System --- Physiological Processes --- Membrane Glycoproteins --- Biochemical Processes --- Membrane Transport Proteins --- Nervous System Physiological Phenomena --- Cell Physiological Processes --- Electrophysiological Phenomena --- Neurons --- Nerve Fibers --- Cell Membrane Structures --- Anatomy --- Cell Membrane --- Biochemical Phenomena --- Membrane Proteins --- Physiological Phenomena --- Carrier Proteins --- Cells --- Musculoskeletal and Neural Physiological Phenomena --- Chemical Processes --- Cell Physiological Phenomena --- Proteins --- Chemical Phenomena --- Phenomena and Processes --- Cellular Structures --- Amino Acids, Peptides, and Proteins --- Chemicals and Drugs --- Neuronal Plasticity --- Synaptic Transmission --- Synapses --- Presynaptic Terminals --- Calcium Channels --- Calcium in the body. --- Channels, Calcium --- Medicine. --- Cell physiology. --- Cell membranes. --- Neurobiology. --- Biomedicine. --- Biomedicine general. --- Membrane Biology. --- Cell Physiology. --- Body composition --- Calcification --- Ion channels --- Cell function --- Cytology --- Physiology --- Cell surfaces --- Cytoplasmic membranes --- Plasma membranes --- Plasmalemma --- Membranes (Biology) --- Glycocalyces --- Neurosciences --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Medical sciences --- Pathology --- Physicians --- Biomedicine, general. --- Health Workforce --- Cell membranes .

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This book is built around ion channel research and, more specifically, ion channels as important therapeutic drug targets. Under the editorial leadership of Gary Stephens in academic research and Edward Stevens from industry, the aim is to bring these strands together to provide a cutting-edge translational reference on ion channel drug discovery. Exploiting our knowledge of ion channel structure and function has clear current and future potential to intervene and correct the pathophysiology associated with debilitating conditions, including cardiovascular disease, diabetes, cystic fibrosis, pain, epilepsy, and neurodegenerative disorders. Individual chapters have a disease focus, also providing a “case study story” that will also appeal to a clinical audience, while background information on a given ion channel is presented to provide a solid reference for undergraduate and postgraduate teaching.

Neurosciences. --- Neurochemistry. --- Pharmacology. --- Neuroscience.