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Mechanisms Of Mode Shift And Gating Polarity In Voltage Dependent Ion Channels
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Book Synopsis Mechanisms of Mode Shift and Gating Polarity in Voltage-dependent Ion Channels by : John Cowgill
Download or read book Mechanisms of Mode Shift and Gating Polarity in Voltage-dependent Ion Channels written by John Cowgill and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Electrical signaling is one of the most essential processes to the survival of higher organisms. This is mediated by the regulated flow of ions through the cell membrane catalyzed by a diverse set of membrane proteins known as ion channels. An important channel type opens and closes in response to changes in the membrane potential. These voltage-gated ion channels (VGICs) thus regulate the very stimulus which governs their activity, enabling them to generate and regulate electrical excitability in cells. In this thesis, I examine the structural and thermodynamic aspects of voltage-dependent regulation of channel function. In Chapter Three, I used a hierarchical approach based on recently-solved cryoEM structures of two VGICs to examine the role of various structural elements in voltage sensing, opening the pore, and coupling these processes. I localized discrete elements in hyperpolarization-activated cyclic nucleotide-regulated (HCN) channels that are responsible for conferring an inverted gating response in these channels compared to virtually all other VGICs which activate on depolarization. Surprisingly, the HCN voltage sensor can gate the same pore open in both hyperpolarizing and depolarizing directions suggesting that these channels use a unique voltage sensing mechanism. In Chapter Four, long-timescale molecular dynamics simulations from collaborators revealed a new atomic model of voltage sensing in HCN channels that sheds light on the mechanism of inverted gating polarity. We experimentally validated this novel mechanism using cysteine accessibility measurements and utilized our bipolar constructs to demonstrate that this mechanism underlies the inverted gating polarity of HCN channels. Finally, in Chapter Five I examined the origin mode shift in VGIC gating, a widely observed phenomenon whereby longterm changes in membrane potential alter gating properties. By improving the protocols for recording gating currents, I demonstrated that the hysteresis in gating charge-voltage relationship that is commonly attributed to mode shift stems from non-equilibrium measurement conditions. Throughout these works, my findings are discussed in terms of structural, functional, and thermodynamic implications.
Book Synopsis Voltage Sensing Mechanism in the Voltage-gated and Proton (H+)-selective Ion Channel Hv1 by : Aaron L. Randolph
Download or read book Voltage Sensing Mechanism in the Voltage-gated and Proton (H+)-selective Ion Channel Hv1 written by Aaron L. Randolph and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Activation of the intrinsic aqueous water-wire proton conductance (GAQ) in Hv1 channels is controlled by changes in membrane potential and the transmembrane pH gradient ([delta]pH). The mechanism by which changes in [delta]pH affect the apparent voltage dependence of GAQ activation is not understood. In order to measure voltage sensor (VS) activation in Hv1, we mutated a conserved Arg residue in the fourth helical segment (S4) to His and measured H+ currents under whole-cell voltage clamp in transfected HEK-293 cells. Consistent with previous studies in VS domain containing proteins, we find that Hv1 R205H mediates a robust resting-state H+ "shuttle" conductance (GSH) at negative membrane potentials. Voltage-dependent GSH gating is measured at more negative voltages than the activation GAQ, indicating that VS activation is thermodynamically distinct from opening of the intrinsic H+ permeation pathway. A hallmark biophysical feature of Hv1 channels is a ~-40 mV/pH unit shift in the apparent voltage dependence of GAQ gating. We show here that changes pHO are sufficient to cause similar shifts in GSH gating, indicating that GAQ inherits its pH dependence from an early step in the Hv1 activation pathway. Furthermore, we show for the first time that Hv1 channels manifest a form of electromechanical coupling VS activation and GAQ pore opening. Second-site mutations of D185 markedly alter GAQ gating without affecting GSH gating, indicating that D185 is required for a late step in the activation pathway that controls opening of the aqueous H+ permeation pathway. In summary, this work demonstrates that the Hv1 activation pathway contains multiple transitions with distinct voltage and pH dependencies that have not been previously identified. The results reported here novel insight into the mechanism of VS activation in Hv1 and raise fundamental questions about the nature of pH-dependent gating and electromechanical coupling in related VS domain-containing ion channels and phosphatases.
Book Synopsis Voltage Gated Sodium Channels by : Peter C. Ruben
Download or read book Voltage Gated Sodium Channels written by Peter C. Ruben and published by Springer Science & Business Media. This book was released on 2014-04-15 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: A number of techniques to study ion channels have been developed since the electrical basis of excitability was first discovered. Ion channel biophysicists have at their disposal a rich and ever-growing array of instruments and reagents to explore the biophysical and structural basis of sodium channel behavior. Armed with these tools, researchers have made increasingly dramatic discoveries about sodium channels, culminating most recently in crystal structures of voltage-gated sodium channels from bacteria. These structures, along with those from other channels, give unprecedented insight into the structural basis of sodium channel function. This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied.
Book Synopsis Molecular Biology of The Cell by : Bruce Alberts
Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Molecular Mechanisms of Voltage-Gating in Ion Channels by : Gildas Loussouarn
Download or read book Molecular Mechanisms of Voltage-Gating in Ion Channels written by Gildas Loussouarn and published by Frontiers Media SA. This book was released on 2021-11-03 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Amiloride-Sensitive Sodium Channels: Physiology and Functional Diversity by :
Download or read book Amiloride-Sensitive Sodium Channels: Physiology and Functional Diversity written by and published by Academic Press. This book was released on 1999-05-04 with total page 425 pages. Available in PDF, EPUB and Kindle. Book excerpt: Sodium reabsorbing epithelia play a major role in whole-body sodium homeostasis. Some examples of sodium regulating tissues include kidney, colon, lung, and sweat ducts. Sodium transport across these membranes is a two-step process: entry through an amiloride-sensitive sodium channel and exit via the ouabain-sensitive sodium/potassium ATPase. The sodium entry channels are the rate-limiting determinant for transport and are regulated by several different hormones. The sodium channels also play a significant role in a number of disease states, like hypertension, edema, drug-induced hyperkalemia, and cystic fibrosis. Amiloride-Sensitive Sodium Channels: Physiology and Functional Diversity provides the first in-depth exchange of ideas concerning these sodium channels, their regulation and involvement in normal and pathophysiological situations. Summarizes current state of amiloride-sensitive sodium channel field Analyzes structure-function of epithelial sodium channels Discusses immunolocalization of epithelial sodium channels Examines hormonal regulation of sodium channels Discusses sodium channels in lymphocytes, kidney, and lung Considers mechanosensitivity of sodium channels Provides ideas on sodium channels and disease
Book Synopsis Annual Proceedings, Reliability Physics by :
Download or read book Annual Proceedings, Reliability Physics written by and published by . This book was released on 1972 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Vertebrate Hair Cells by : Ruth Eatock
Download or read book Vertebrate Hair Cells written by Ruth Eatock and published by Springer Science & Business Media. This book was released on 2006-07-01 with total page 465 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Springer Handbook of Auditory Research presents a series of compreh- sive and synthetic reviews of the fundamental topics in modern auditory - search. The volumes are aimed at all individuals with interests in hearing research including advanced graduate students, postdoctoral researchers, and clinical investigators. The volumes are intended to introduce new investigators to important aspects of hearing science and to help established investigators to better understand the fundamental theories and data in ?elds of hearing that they may not normally follow closely. Each volume presents a particular topic comprehensively, and each serves as a synthetic overview and guide to the literature. As such, the chapters present neither exhaustive data reviews nor original research that has not yet appeared in peer-reviewed journals. The volumes focus on topics that have developed a solid data and conceptual foundation rather than on those for which a literature is only beginning to develop. New research areas will be covered on a timely basis in the series as they begin to mature.
Download or read book Piezo Channels written by and published by Academic Press. This book was released on 2017-07-17 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: Piezo Channels, Volume 79, the latest volume in the Current Topics in Membranes series provides the necessary membrane research to assist readers in discovering the current state of a particular field and future directions. New chapters in the updated volume include A Tour de Force: The Discovery, Properties, and Function of Piezo Channels, Piezo1 Channels in Vascular Development and the Sensing of Shear Stress, the Origin of the Force: The Force-From-Lipids Principle Applied to Piezo Channels, Genetic Diseases of PIEZO1 and PIEZO2 Dysfunction, and The Structural Basis for Sensing by the Piezo1 Protein. Users of this series will find an up-to-date presentation of the current knowledge in the field of Piezo Channels. Written by leading experts in the field Contains original material, both textual and illustrative, that make it a very relevant reference Presented in a very comprehensive manner Ideal reference for both researchers in the field and general readers who will find this book to be relevant and up-to-date
Book Synopsis Lippincott® Illustrated Reviews: Physiology by : Robin R. Preston
Download or read book Lippincott® Illustrated Reviews: Physiology written by Robin R. Preston and published by Lippincott Williams & Wilkins. This book was released on 2018-12-26 with total page 544 pages. Available in PDF, EPUB and Kindle. Book excerpt: Publisher's Note: Products purchased from 3rd Party sellers are not guaranteed by the Publisher for quality, authenticity, or access to any online entitlements included with the product. Enhanced by a new chapter, new illustrations, and new Q&As, LIppincott® Illustrated Reviews: Physiology, Second Edition brings physiology clearly into focus, telling the story of who we are; how we live; and, ultimately, how we die. By first identifying organ function and then showing how cells and tissues are designed to fulfill that function, this resource decodes physiology like no other text or review book. Tailored for ease of use and fast content absorption, the book’s outline format, visionary artwork, clinical applications, and unit review questions help students master the most essential concepts in physiology, making it perfect for classroom learning and test and boards preparation.
Book Synopsis Mechanosensitive Ion Channels, Part A by :
Download or read book Mechanosensitive Ion Channels, Part A written by and published by Elsevier. This book was released on 2011-09-21 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: Current Topics in Membranes provides a systematic, comprehensive, and rigorous approach to specific topics relevant to the study of cellular membranes. Each volume is a guest edited compendium of membrane biology. This series has been a mainstay for practicing scientists and students interested in this critical field of biology. Articles covered in the volume include The Mechanical Properties of Bilayers; Molecular Dynamic Modeling of MS Channels; Structures of the Prokaryotic Mechanosensitive; Channels MscL and MscS; 3.5 Billion Years of Mechanosensory Transduction: Structure and Function of Mechanosensitive Channels in Prokaryotes; Activation of Mechanosensitive Ion Channels by Forces Transmitted through Integrins and the Cytoskeleton; Thermodynamics of Mechanosensitivity; Flexoelectricity and Mechanotransduction; Lipid Effects on Mechanosensitive Channels; Functional Interactions of the Extracellular Matrix with Mechanosensitive Channels; MSCL: The Bacterial Mechanosensitive Channel of Large Conductance; The Bacterial Mechanosensitive Channel MscS: Emerging Principles of Gating and Modulation; Structure function relations of MscS; The MscS Cytoplasmic Domain and its Conformational Changes upon the Channel Gating; Microbial TRP Channels and Their Mechanosensitivity; MSCS-Like Proteins in Plants; Delivering Force and Amplifying Signals in Plant Mechanosensing; MS Channels in Tip Growing Systems.
Book Synopsis Cell-Cell Channels by : František Baluška
Download or read book Cell-Cell Channels written by František Baluška and published by Springer Science & Business Media. This book was released on 2006-08-28 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers cell-cell channels at all levels of biological organization. The purpose of this book is to document that cells are not physically separated and fully autonomous units of biological life as stated by the currently valid Cell Theory. If not the cell then some lower level unit must fulfill this role. The book deals also with the identity of this elusive unit of biological life.
Book Synopsis Japanese Journal of Applied Physics by :
Download or read book Japanese Journal of Applied Physics written by and published by . This book was released on 2000 with total page 1312 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Cardiac Mechano-electric Feedback and Arrhythmias by : Peter Kohl
Download or read book Cardiac Mechano-electric Feedback and Arrhythmias written by Peter Kohl and published by Saunders. This book was released on 2005 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt: Kohl (Cardio Mechano-Electric Feedback Lab, Oxford University) documents the role of mechano-electric feedback (MEF) in electrical and mechanical pathological remodeling of cardiac function. Sections cover sub-cellular mechanisms of cardiac MEF, effects of MEF on cardiac cellular electrophysiology, experimental manifestations of MEF in the heart, cardiac MEF in normal physiology, cardiac MEF as a pathogenic mechanism, MEF as a mechanism involved in therapeutic interventions, and the outlook for the future. B&w and color photos and medical images are included. Annotation: 2005 Book News, Inc., Portland, OR (booknews.com).
Book Synopsis Textbook of Membrane Biology by : Rashmi Wardhan
Download or read book Textbook of Membrane Biology written by Rashmi Wardhan and published by Springer. This book was released on 2018-01-10 with total page 385 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive overview of the basic principles, concepts, techniques and latest advances in the field of biomembranes and membrane-associated processes. With new emerging technologies and bioinformatics tools, this is a promising area for future study and research. The book discusses the composition, fluidity and dynamic nature of phospholipid bilayers, which vary with cell/organelle type and function. It describes the various types of transport proteins that facilitate the transport of polar and nonpolar molecules across the membrane actively or passively via ion-channels or through porins. It also explores the many cellular functions membranes participate in: (1) energy transduction, which includes the electron transport chain in inner membrane of mitochondria and bacterial cytoplasmic membrane and photosynthetic electron transport in thylakoid membranes in chloroplast and photosynthetic bacterial membranes; (2) cell–cell communication involving various signal transduction pathways triggered by activated membrane receptors; (3) cell–cell interactions involving various types of adhesion and receptor proteins; (4) nerve transmission involving opening and closing of voltage gated ionic channels; and (5) intracellular transport involving the processes of endocytosis, exocytosis, vesicular transport of solutes between intracellular compartments, membrane fusion and membrane biogenesis.
Book Synopsis Organellar Ion Channels and Transporters by : Barbara E. Ehrlich
Download or read book Organellar Ion Channels and Transporters written by Barbara E. Ehrlich and published by . This book was released on 1996 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Extrasynaptic GABAA Receptors by : Adam C. Errington
Download or read book Extrasynaptic GABAA Receptors written by Adam C. Errington and published by Springer. This book was released on 2014-09-22 with total page 301 pages. Available in PDF, EPUB and Kindle. Book excerpt: GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor-mediated inhibition, termed “tonic” inhibition, has been described. Whereas synaptic GABAA receptors underlie classical “phasic” GABAA receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This book highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.