Progress Towards an Understanding of Voltage-sensing in Ion Channels PDF Download

Author: Chris Shrenik Gandhi
Publisher:
ISBN:
Category :
Languages : en
Pages : 402

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Author: Frances M. Ashcroft
Publisher: Academic Press
ISBN: 0080535216
Category : Science
Languages : en
Pages : 505

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Book Description
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

Author: Jakob Renhorn
Publisher: Linköping University Electronic Press
ISBN: 9176853381
Category :
Languages : en
Pages : 71

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Book Description
Voltage-gated ion channels have a paramount importance in many physiological processes such as cell-to-cell communication, action potential-propagation, and cell motility. Voltage-gated ion channels are characterized by their ability to sense membrane voltage and to greatly change channel activity in response to small changes in the voltage. The ability to sense voltage resides in the four voltage-sensor domains (VSDs) surrounding the central ion-conducting pore. Membrane depolarization causes the inside of the membrane to become positively charged, electrostatically repelling the positively charged fourth transmembrane segment (S4), or voltage sensor, in the VSD, causing the voltage sensor to move outwards. This motion provides necessary energy to open the pore and allow ion conductivity. Prolonged channel activation leads to alterations in the selectivity filter which cease ion conductivity, in a process called slow inactivation. In this thesis, we investigated the movement of S4 during activation of the channel. We also studied the communication between the four subunits during activation as well as the communication between the pore domain and VSD during slow inactivation. We have shown that voltage sensors move approximately 12 Å outwards during activation. The positively charged amino acid residues in S4 create temporary salt bridges with negative counter-charges in the other segments of the VSD as it moves through a membrane. We have also shown that the movement of one of the four voltage sensors can affect the movement of the neighboring voltage sensors. When at least one voltage sensor has moved to an up-position, it stabilizes other voltage sensors in the up-position, increasing the energy required for the voltage sensor to return to the down position. We have also shown reciprocal communication between the pore domain and the VSDs. Alterations in the VSD or the interface between the pore and the VSD cause changes in the rate of slow inactivation. Likewise, modifications in the pore domain cause changes to the voltage-sensor movement. This indicates communication between the pore and the VSD during slow inactivation. The information from our work could be used to find new approaches when designing channel-modifying drugs for the treatment of diseases caused by increased neuronal excitability, such as chronic pain and epilepsy.

Author: Boris Martinac
Publisher: Springer Science & Business Media
ISBN: 3540727396
Category : Science
Languages : en
Pages : 322

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This is the first book that is not exclusively focused on ion channels functioning in sensory mechanisms that are characteristic of animals and humans, but also describes the role of ion channels in signal transduction mechanisms found in microbial cells and plants. It summarizes comprehensively the progress that has been made in studies of ion channels and their role in sensory physiology.

Author: Kevin M. Oelstrom
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Book Description
Complex multicellular organisms need a communication network that links distant parts of the organism and allows information to be rapidly transmitted between these regions. This task is accomplished by electrochemical signaling through excitable cells and is regulated by ion channels that allow selective passage of different charged species through their transmembrane pores depending on numerous conditions. A specific kind of ion channel, a voltage-gated ion channel, allows sodium, calcium or potassium to move across either side of the membrane when a change in the membrane potential directly influences the channel and ultimately opens its pore gate. This thesis focuses on two aspects of this process; the location and composition of the gate in a voltage-dependent sodium channel and the mechanism by which a change in voltage can be sensed by a channel and then have this information transmitted through the protein to the gate, prompting it to open. By substituting individual cysteine residues into the lower S6 helices of domains I-IV of a voltage-gated sodium channel and measuring their state-dependent accessibility to a membrane-impermeant thiol-modifying reagent, it was demonstrated that the gate in this channel type is located near the cytoplasmic end of the pore and is minimally composed of four bulky hydrophobic amino acids. After measuring gating currents for numerous single and double alanine mutant pairs and using this information to calculate the change in free energy of activation for each mutant, multiple interaction networks were identified in different regions of the Shaker potassium channel that are involved in the process of transmitting the energy associated with voltage-sensing to the channel gate. Results will be discussed within the context of relevant structural information.

Author: Wolfgang B. Liedtke, MD, PH.D.
Publisher: CRC Press
ISBN: 1420005847
Category : Medical
Languages : en
Pages : 502

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Book Description
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

Author: Bruce Alberts
Publisher:
ISBN: 9780815332183
Category : Cytology
Languages : en
Pages : 0

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Author: Jie Zheng
Publisher: CRC Press
ISBN: 1466551429
Category : Medical
Languages : en
Pages : 682

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Book Description
The New Benchmark for Understanding the Latest Developments of Ion ChannelsIon channels control the electrical properties of neurons and cardiac cells, mediate the detection and response to sensory stimuli, and regulate the response to physical stimuli. They can often interact with the cellular environment due to their location at the surface of ce

Author: Jie Zheng
Publisher: CRC Press
ISBN: 1000857751
Category : Medical
Languages : en
Pages : 331

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Book Description
The Textbook of Ion Channels is a set of three volumes providing a wide-ranging reference source on ion channels for students, instructors and researchers. Ion channels are membrane proteins that control the electrical properties of neurons and cardiac cells; mediate the detection and response to sensory stimuli like light, sound, odor, and taste; and regulate the response to physical stimuli like temperature and pressure. In non-excitable tissues, ion channels are instrumental for the regulation of basic salt balance that is critical for homeostasis. Ion channels are located at the surface membrane of cells, giving them the unique ability to communicate with the environment, as well as the membrane of intracellular organelles, allowing them to regulate internal homeostasis. Ion channels are fundamentally important for human health and diseases, and are important targets for pharmaceuticals in mental illness, heart disease, anesthesia, pain and other clinical applications. The modern methods used in their study are powerful and diverse, ranging from single ion-channel measurement techniques to models of ion channel diseases in animals, and human clinical trials for ion channel drugs. Volume I, Part 1 covers fundamental topics such as the basic principles of ion permeation and selectivity, voltage-dependent, ligand-dependent, and mechano-dependent ion channel activation mechanisms, the mechanisms for ion channel desensitization and inactivation, and basic ion channel pharmacology and inhibition. Volume I, Part 2 offers a practical guide of cardinal methods for researching ion channels, including heterologous expression and voltage-clamp and patch-clamp electrophysiology; isolation of native currents using patch clamping; modeling ion channel gating, structures, and its dynamics; crystallography and cryo-electron microscopy; fluorescence and paramagnetic resonance spectroscopy methods; and genetics approaches in model organisms. All three volumes give the reader an introduction to fundamental concepts needed to understand the mechanism of ion channels; a guide to the technical aspects of ion channel research; a modern guide to the properties of major ion channel families; and includes coverage of key examples of regulatory, physiological and disease roles for ion channels.

Author: H. Richard Leuchtag
Publisher: Springer Science & Business Media
ISBN: 1402055250
Category : Science
Languages : en
Pages : 545

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Book Description
Voltage-sensitive ion channels are macromolecules embedded in the membranes of nerve and muscle fibers of animals. Despite decades of intensive research under the traditional approach of gated structural pores, the relation between the structure of these molecules and their function remains enigmatic. This book examines physically oriented approaches not covered in other ion-channel books, and it develops a new physics-based approach to the problem of molecular excitability.