A volume in the Molecular and Cellular Neurobiology series. This book reviews the recent advances in our understanding of the molecular and cellular mechanisms that control the assembly, transport, targeting and anchoring of the protein complexes making up the most important ion channels and receptor families, fundamental to synaptic function. Improved understanding of these processes is expected to reveal novel therapeutic targets relevant to a range of disease states. The first section of the book contains three chapters dealing with cation channels and provides an accessible, succinct and comprehensive account of what is known about the structures and the assembly and targeting of these multimeric proteins. The focus of the book then moves on to cover ligand-gated ion channels with two chapters on accetylcholine receptors. The final section of the book contains four chapters covering the excitatory and inhibitory amino acid receptors. Receptor and Ion-Channel Trafficking provides an integrated overview of the significant recent advances in the field of molecular neurobiology and will be essential reading for all researchers in neuroscience, neurobiology, biochemistry, cellular and molecular biology.

Protein sorting and trafficking are regulated by well-conserved mechanisms. These allow a distinctive set of resident proteins to be present in the correct subcellular organelle, which is required for proper cell functioning. Voltage-gated ion channels, as responsible for cardiomyocyte action potential, must be properly localized. They participate in cell excitability and electrical coupling, ensuring uninterrupted and rhythmic heart beating. Ion channel complexes comprise one or more pore-forming α subunits, associated β subunits, and additional proteins. Channel localization and function are regulated by the β subunits and associated proteins, such as cytoskeletal elements, cell-adhesion molecules, and adaptors. These influence protein targeting, anchoring, and retention in specific surface domains along the cardiomyocyte sarcolemma, such as intercalated discs, T-tubules, or the lateral membrane. Alterations in ion channel trafficking are the cause of channelopathies associated with inherited arrhythmias leading to sudden death. An outstanding question is how these molecular alterations lead to disease. In this volume, scientists share their vision to understand how cardiac ion channel trafficking is regulated and how it may become altered, leading to channelopathies that often turn into deadly arrhythmias. Data generated can be translated to a clinical context, hopefully turning into approaches to help prevention and treatment, which is of utmost importance, both medically and socially.

Since the first TRP ion channel was discovered in Drosophila melanogaster in 1989, the progress made in this area of signaling research has yielded findings that offer the potential to dramatically impact human health and wellness. Involved in gateway activity for all five of our senses, TRP channels have been shown to respond to a wide range of st

In the search for simple explanations of the natural world, its complicated textures are often filed down to a smoothened surface of our liking. The impetus for this Research Topic was borne out of a need to re-ignite interest in the complex – in this case in the context of ion channels in the nervous system. Ion channels are the large proteins that form regulated pores in the membranes of cells and, in the brain, are essential for the transfer, processing and storage of information. These pores full of twists and turns themselves are not just barren bridges into cells. More and more we are beginning to understand that ion channels are like bustling medieval bridges (packed with apartments and shops) rather than the more sleek modern variety – they are dynamic hubs connected with many structures facilitating associated activities. Our understanding of these networks continues to expand as our investigative tools advance. Together these articles highlight how the complexity of ion channel signaling nexuses is critical to the proper functioning of the nervous system.

Ion Channels, Part C, Volume 653 in the Methods in Enzymology series, highlights new advances in the field with this new volume presenting interesting chapters on a variety of topics, including Nonsense suppression in ion channels, Engineering Ion Channels Using Protein Trans-splicing, Probing Ion Channel Neighborhoods Using APEX, STX based probes for NaVs, ANAP: a versatile, fluorescent probe of ion channel gating and regulation, High Throughput Screens for Small Molecule Ion Channel Modulators, Using toxins to study ion channels, Re/de-constructing ubiquitin regulation of ion channels, Tethered Peptide Toxins for Ion Channels, Voltage-Sensing Phosphatase Molecular Engineering, and more. Additional chapters cover Engineering excitable cells, Stretch and Poke Stimulation of Mechanically-Activated Ion Channels, Optical Control of STIM Channels, High Throughput Electrophysiological Evaluation of Mutant Ion Channels, Evaluating BEST1 Mutations in RPE Stem Cells, Long Read Transcript Profiling of Ion Channel Splice Variants, Permeation of Connexin Channels, Ratiometric pH indicator for melanosomes and lysosomes, and Ion channels in the epithelial cells of the choroid plexus. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series

Ion channels are membrane proteins that act as gated pathways for the movement of ions across cell membranes. They play essential roles in the physiology of all cells. In recent years, an ever-increasing number of human and animal diseases have been found to result from defects in ion channel function. Most of these diseases arise from mutations in the genes encoding ion channel proteins, and they are now referred to as the channelopathies. Ion Channels and Disease provides an informative and up-to-date account of our present understanding of ion channels and the molecular basis of ion channel diseases. It includes a basic introduction to the relevant aspects of molecular biology and biophysics and a brief description of the principal methods used to study channelopathies. For each channel, the relationship between its molecular structure and its functional properties is discussed and ways in which genetic mutations produce the disease phenotype are considered. This book is intended for research workers and clinicians, as well as graduates and advanced undergraduates. The text is clear and lively and assumes little knowledge, yet it takes the reader to frontiers of what is currently known about this most exciting and medically important area of physiology. Introduces the relevant aspects of molecular biology and biophysics Describes the principal methods used to study channelopathies Considers single classes of ion channels with summaries of the physiological role, subunit composition, molecular structure and chromosomal location, plus the relationship between channel structure and function Looks at those diseases associated with defective channel structures and regulation, including mutations affecting channel function and to what extent this change in channel function can account for the clinical phenotype