ATP-gated P2X receptors in health and disease

ATP-gated P2X receptors in health and disease

Author: Andrea Nistri

Publisher: Frontiers Media SA

Published: 2015-01-05

Total Pages: 173

ISBN-13: 2889194051

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Extracellular ATP is currently recognized as one of the most widely distributed neurotransmitters and neuromodulators in the peripheral and central nervous system. ATP-gated P2X receptors are expressed by neurons, glial and many other non-neuronal cells and represent an attractive target for therapeutic interventions. Diverse molecular and cellular mechanisms have been identified for P2X receptor functioning, including the ability to enlarge the size of the ion pore associated with the release of several key immune molecules. A major recent breakthrough was the determination of the X-ray crystal structures of zebrafish P2X4 receptor in ATP-bound and ATP-free states. The P2X receptor research field is rapidly growing, as evidenced by the almost 2000 papers published in the last 5 years. However, despite the fundamental signalling function of extracellular ATP in the nervous system, the widespread roles of P2X receptors have not been widely elucidated and presented in textbooks. In this volume of papers we aim to gather a collection of high quality papers, detailing the latest insights from the most accomplished international P2X receptor researchers. Importantly, basic research into P2X receptors has a strong translational impact and our collection of articles could be a valuable guide for the development of new pharmacological and biotechnological tools addressing the function of P2X receptors. Within this collection we plan to cover receptor structure-function relationships, receptors trafficking, to highlight the special properties of P2X receptors and their pharmacological profiles, and to describe the translational aspects of cellular ATP signaling in pain and in other neurological and vascular diseases.


Receptors P1 and P2 as Targets for Drug Therapy in Humans

Receptors P1 and P2 as Targets for Drug Therapy in Humans

Author: Robson Faria

Publisher: BoD – Books on Demand

Published: 2020-03-11

Total Pages: 112

ISBN-13: 1789845343

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This book aims to provide a brief update on the functions of purinergic receptors in various systems, in addition to the signaling pathway activated to mediate these functions. We address the influence of hypoxia by modulating the activity of these receptors under physiological and pathophysiological conditions. Additionally, we describe the mechanisms of induction of pain and inflammation in different systems. Finally, the book discusses some of the main bioinformatics tools currently used to improve or discover new prototypes capable of selectively acting on these receptors with estimated parameters of satisfactory solubility and toxicity for possible commercial implementation.


Ion Channels and Disease

Ion Channels and Disease

Author: Frances M. Ashcroft

Publisher: Academic Press

Published: 1999-10-20

Total Pages: 505

ISBN-13: 0080535216

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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


Ion Channel Regulation

Ion Channel Regulation

Author:

Publisher: Academic Press

Published: 1999-04-13

Total Pages: 339

ISBN-13: 0080526454

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Volume 33 reviews the current understanding of ion channel regulation by signal transduction pathways. Ion channels are no longer viewed simply as the voltage-gated resistors of biophysicists or the ligand-gated receptors of biochemists. They have been transformed during the past 20 years into signaling proteins that regulate every aspect of cell physiology. In addition to the voltage-gated channels, which provide the ionic currents to generate and spread neuronal activity, and the calcium ions to trigger synaptic transmission, hormonal secretion, and muscle contraction, new gene families of ion channel proteins regulate cell migration, cell cycle progression, apoptosis, and gene transcription, as well as electrical excitability. Even the genome of the lowly roundworm Caenorhabditis elegans encodes almost 100 distinct genes for potassium-selective channels alone. Most of these new channel proteins are insensitive to membrane potential, yet in humans, mutations in these genes disrupt development and increase individual susceptibility to debilitating and lethal diseases.How do cells regulate the activity of these channels? How might we restore their normal function? In Ion Channel Regulation, many of the experts who pioneered these discoveries provide detailed summaries of our current understanding of the molecular mechanisms that control ion channel activity. Reviews brain functioning at the fundamental, molecular level Describes key systems that control signaling between and within cells Explains how channels are used to stimulate growth and changes to activity of the nucleus and genome


The Oxford Handbook of Neuronal Ion Channels

The Oxford Handbook of Neuronal Ion Channels

Author: Arin Bhattacharjee

Publisher: Oxford University Press

Published: 2023-01-02

Total Pages: 785

ISBN-13: 0190669160

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Neurons are excitable cells. They use ions and electrical signaling to talk to each to other and when they talk to each other, neurons control behavior. The Oxford Handbook of Neuronal Ion Channels is an accessible reference describing the nature and properties of ion channels in neurons. The book explains how ion channels open and close, how they can be selective for specific ions, and how they give rise to action potentials. Included are in-depth chapters discussing specific classes of ion channels: potassium channels, sodium channels, neurotransmitter-gated ion channels and other specialized channels. Throughout the handbook, important insight is provided on the contribution ion channels make to neuronal excitability and to synaptic transmission. The handbook goes further to discuss channelopathies, a group of human diseases such as epilepsy, pain and migraines that can be caused by ion channel dysfunction. For neuroscientists, biophysicists and neuropharmacologists, this handbook is a valuable reference of ion channel biology and function.


Biased Signaling in Physiology, Pharmacology and Therapeutics

Biased Signaling in Physiology, Pharmacology and Therapeutics

Author: Brian J Arey

Publisher: Elsevier

Published: 2014-06-05

Total Pages: 317

ISBN-13: 0124115071

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Biased Signaling in Physiology, Pharmacology and Therapeutics is a unique and essential reference for the scientific community concerning how conformational-dependent activation is a common phenomenon across many classes of receptors or signaling molecules. It discusses the role of conformational dynamics in leading to signaling bias across different classes of receptors and signaling molecules. By providing a broader view of signaling bias, this resource helps to explain common mechanisms shared across receptor classes and how this can be utilized to elucidate their cellular activity and better understand their therapeutic potential. Written for both new and established scientists in pharmacology, cell biology, biochemistry, and signal transduction, as well as physicians, this book clearly illustrates how biased receptor signaling can be utilized to develop and understand complex pharmacology. Chapters are each focused on a specific class of receptor or other important topic and make use of real-world examples illustrating how the latest research in signal transduction has led to a better understanding of pharmacology and cell biology. This structure creates a basis for understanding that physiological signalling bias has been selected by nature in order to provide complex and tissue- specific biological responses in the face of limited receptors and signaling pathways. This book provides a framework to reveal that these physiological mechanisms are not restricted to one receptor type or family and thus presents receptor signaling from a newer, more global perspective. Offers a unique and valuable resource on biased receptor signaling that provides a global view for better understanding pharmacology across many receptor families Integrates biased receptor signaling, physiology, and pharmacology to place this emerging science within the context of treating disease Includes important chapters on both the pharmaceutical and therapeutic implications of biased signaling


The P2X7 Receptor

The P2X7 Receptor

Author: Annette Nicke

Publisher: Springer Nature

Published: 2022-07-01

Total Pages: 401

ISBN-13: 1071623842

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This detailed volume covers diverse aspects of P2X7 receptor analysis, ranging from its molecular structure to related pharmacological and immunological tools, via its analysis in heterologous expression systems as well as assays using primary cells and whole animal models. After three introductory chapters that focus on its structure, ligands, and physiological functions, the book details the generation of antibody and nanobody tools for P2X7 receptors, provides protocols for the analysis of expressed P2X7 receptors with a focus on their electrophysiological analysis, as well as protocols for the investigation of P2X7 down-stream signaling in immune cells by flow cytometry. Mouse models and procedures suited to investigate P2X7-mediated effects in other primary cells and in vivo are also explained. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, The P2X7 Receptor: Methods and Protocols is a valuable reference not only for the growing community fascinated by this unusual ion channel but also for a broad readership interested in ion channels or purinergic receptors.