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Дисертації з теми "Ion channels Molecular aspects"

Автор: Grafiati

Опубліковано: 4 червня 2021

Оновлено: 28 січня 2023

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1

Qiu, Min Ru Clinical School of Medicine St Vincent's Hospital UNSW. "Functional and molecular aspects of ion channels in macrophages." Awarded by:University of New South Wales. Clinical School of Medicine, St. Vincent's Hospital, 2003. http://handle.unsw.edu.au/1959.4/20442.

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Monocytes/macrophages play very important roles in innate and adaptive immunity. Ion channels are small molecules embedded in the cell membrane and they play fundamental roles in cell function. Both topics have been extensively studied in isolation, however the role of ion channels in macrophage function is far less understood. In this thesis, the functional and molecular aspects of two ion channels expressed in macrophages, Kor, a potassium channel, and CLIC1, a chloride channel were studied. The biological function of Kor and CLIC1 in activated human macrophages was examined using ion channe

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2

Corry, Ben Alexander. "Simulation studies of biological ion channels." View thesis entry in Australian Digital Theses Program, 2002. http://thesis.anu.edu.au/public/adt-ANU20030423.162927/index.html.

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3

Amiri, Shiva. "Computational modelling and molecular dynamics simulations of ligand-gated ion channels." Thesis, University of Oxford, 2006. http://ora.ox.ac.uk/objects/uuid:119c7ccb-e7b2-4da1-a137-40c3289c3ad8.

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Torpedo AChR structure was used to make models of other LGICs. Coarse-grain MD allowed the identification of residues in the TM domain interacting with the lipid-bilayer. Born energy profiles through LGIC pores reveal that the EC domain plays a key role in ion selectivity.

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4

Hedley, Paula Louise. "Molecular and functional characterisation of Long QT Syndrome causing genes." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/86480.

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Thesis (PhD)-- Stellenbosch University, 2014.<br>ENGLISH ABSTRACT: Ventricular arrhythmias are the most important cause of sudden cardiac death (SCD) among adults living in industrialised nations. Genetic factors have substantial effects in determining population-based risk for SCD and may also account for inter-individual variability in susceptibility. Great progress has been made in identifying genes underlying various Mendelian disorders associated with inherited arrhythmia susceptibility. The most well studied familial arrhythmia syndrome is the congenital long QT syndrome (LQTS) caused by

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5

Breed, Jason. "Molecular modelling of ion channels." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308690.

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6

Zhou, Xin. "Towards voltage-gated ion channels, molecular diodes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0012/NQ32730.pdf.

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7

Bjelkmar, Pär. "Modeling of voltage-gated ion channels." Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-63437.

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The recent determination of several crystal structures of voltage-gated ion channels has catalyzed computational efforts of studying these remarkable molecular machines that are able to conduct ions across biological membranes at extremely high rates without compromising the ion selectivity. Starting from the open crystal structures, we have studied the gating mechanism of these channels by molecular modeling techniques. Firstly, by applying a membrane potential, initial stages of the closing of the channel were captured, manifested in a secondary-structure change in the voltage-sensor. In a f

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8

Adcock, Charlotte. "Molecular modelling and electrostatic properties of ion channels." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297941.

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9

Bahnasi, Yahya Mohamed. "Molecular physiology and pharmacolgy of TRPC5 ion channels." Thesis, University of Leeds, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496554.

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10

Elliott, David James Stuart. "Molecular mechanisms of voltage sensing by ion channels." Thesis, University of Leeds, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406206.

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11

Verdin, Paul Stephen. "Molecular interactions of pyrethroid insecticides with insect ion channels." Thesis, University of Nottingham, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.495529.

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Much of the present knowledge of the activity of pyrethroids on the insect Na⁺ channel has come from the electrophysiological investigation of Na⁺ channels expressed heterologously in the Xenopus laevis oocyte expression system. The effects of the naturally occurring pyrethroid resistance mutations, located within the Na⁺ channel gene(s), have also been studied in this way. These studies have yielded a wealth of information, but make several assumptions - that insect Na⁺ channels behave normally in this alien environment and that the expressed channels accurately represent the range channels p

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12

Dayl, Sudad Amer. "Molecular modelling of ATP-gated P2X receptor ion channels." Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/42761.

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P2X receptors (P2XRs) are trimeric cation channels activated by extracellular ATP. Human P2XRs (P2X1-7) are expressed in nearly all mammalian tissues, and they are an important drug target because of their involvement in inflammation and neuropathic pain. The aim of this thesis is to address the following questions. P2XR crystal structures have revealed an unusual U-shape conformation for bound ATP; how does the U-shape conformation of ATP and its derivatives affect channel activation? Where and how do the selective, non-competitive inhibitors AZ10606120 and A438079 bind to P2X7R? What is the

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13

Ta, Chau My. "Molecular pharmacology of native and exogenous vascular ion channels." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:798b4303-12d5-40b2-a850-0a68a03865a1.

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Vascular Ca<sup>2+</sup>-activated chloride channels (CaCCs), are a class of ligand- and voltage-gated channels that couple agonist binding and inositol triphosphate (IP3) signalling to depolarisation of the cell membrane and smooth muscle contraction. The elucidation of the precise physiological role and the pharmacological profile of this channel has been accelerated by the recent discovery of the gene (TMEM16A) coding for these channels. Based on the rationale that depolarising membrane potential (V<sub>m</sub>) causes contraction in vascular SMCs, the possibility of controlling vessel tone

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14

Mustafa, Morad. "Ion Permeation through Membrane Channels: Molecular Dynamics Simulations Studies." Diss., CLICK HERE for online access, 2008. http://contentdm.lib.byu.edu/ETD/image/etd2477.pdf.

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15

Nilsson, Johanna. "Molecular mechanisms of local anaesthetic action on voltage-gated ion channels /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-748-7/.

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16

Broomand, Amir. "Molecular aspects on voltage-sensor movement." Doctoral thesis, Linköping : Univ, 2007. http://www.bibl.liu.se/liupubl/disp/disp2007/med1028s.pdf.

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17

Gwan, Jean-Fang. "The molecular mechanism of multi-ion conduction in K+ channels." [S.l.] : [s.n.], 2007. http://deposit.ddb.de/cgi-bin/dokserv?idn=983151253.

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18

Wei, Xiaomei. "Investigating Meningeal Ion Channels As New Molecular Targets For Migraine." Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/565832.

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This dissertation will present the four manuscripts I published or am ready to publish on the study of the pathophysiology of migraine headache. The first chapter will discuss the background of the current understanding of migraine pathophysiology. Chapter 2 is focused on studying how Transient receptor potential vanilloid 4 (TRPV4) might play a role in migraine headache. Chapter 3 is the study of a novel cell type: dural fibroblasts might also play an active role in migraine headache. Chapter 4 is discussing Norepinephrine's role in headache pathophysiology. Chapter 5 is studying the combined

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19

Liang, Jieming, and 梁捷明. "Physiology of acupuncture: a study of mechanosensitive ion channels." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45451709.

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20

Mullapudi, Laxmi. "A PARALLEL MOLECULAR DYNAMICS PROGRAM FOR SIMULATION OF WATER IN ION CHANNELS." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1789.

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With a modest beginning from developing a model of dynamics of hard liquid spheres (Alder et al., 1957), molecular dynamics (MD) simulations have come to a point where complex biomolecules can be simulated with precision close to reality (Noskov et al., 2007). In this context, a parallel molecular dynamics program for simulation of ion channels associated with cellular membranes has been developed. The parallel MD code developed is simple, efficient, and easily coupled to other codes such as the hybrid molecular dynamics/ brownian dynamics (MD/BD) code developed for the study of protein inter

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21

Forster, Christine. "Aspects of charge exchange in ion-atom collisions." Thesis, Durham University, 1990. http://etheses.dur.ac.uk/6189/.

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The straight line semi-classical Impact Parameter method has been modified for use with classical trajectories. Ion-atom collisions have been modelled using wavefunctions expanded in terms of atomic basis states which were centred on either the target or projectile ions. Total and differential charge exchange cross-sections are presented for (^4)He(^++) and (^4)He(^+) collisions within the centre of mass energy range 0.21 kev < E(_em) < 2.5 keV. Results using curved and straight line paths are compared with data from other authors. Significant trajectory effects were found at the lower energie

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22

Lange, Michael. "Competition between reaction channels in electron collisions of the hydrogen molecular ion HD+." [S.l. : s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=962794775.

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23

Araújo, Rúbia Aparecida de. "Molecular actions of pyrethroids on ion channels in the maize weevil, Sitophilus zeamais." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/11604/.

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Previous studies on the mechanism of action of pyrethroids have confirmed that voltage-gated sodium channels (VGSC) in the axon membrane are the major target site of these compounds. The use of pyrethroids to control maize weevils, Sitophilus zeamais, a major pest of stored maize in Brazil, has led to the occurrence of resistance. The work described here seeks to establish whether changes in VGSC of S.zeamais can explain pyrethroid resistance. The S. zeamais homologue of the Drosophila para VGSC was identified using degenerate primers and sequenced. Resistance mutations were examined by sequen

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24

Cifelli, Carlo. "Impairment of force development in K(ATP) channel deficient skeletal muscle involves calcium ion influx through L-type calcium ion channels." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27342.

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ATP-sensitive potassium (KATP) channels link membrane excitability to metabolism. They are regulated by intracellular nucleotides and other factors, and have been shown to play a role in development of skeletal muscle force, but controversy surrounds their role during fatigue. The aim of this research project was to determine the role of KATP channel under conditions that allow for better assessment of changes in force during fatigue, by virtue of using a smaller whole muscle model less subject to anoxia. Thus, the first objective was to determine the effect of the loss of KATP channel activit

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25

Schmidt, Matthias Rene. "K+ channels : gating mechanisms and lipid interactions." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:51dc4149-d943-4dcd-bf5b-f04130456d84.

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Computational methods, including homology modelling, in-silico dockings, and molecular dynamics simulations have been used to study the functional dynamics and interactions of K<sup>+</sup> channels. Molecular models were built of the inwardly rectifying K<sup>+</sup> channel Kir2.2, the bacterial homolog K<sup>+</sup> channel KirBac3.1, and the twin pore (K2P) K<sup>+</sup> channels TREK-1 and TRESK. To investigate the electrostatic energy profile of K<sup>+</sup> permeating through these homology models, continuum electrostatic calculations were performed. The primary mechanism of KirBac3.1

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26

Naylor, S. "Applications and mechanistic aspects of fast atom bombardment mass spectroscopy." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234018.

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27

Rosenberg, Madelaine. "Factors that influence the expression of neurotransmitter-gated ion channels on developing peripheral neurons." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0019/NQ44563.pdf.

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28

Livesey, Matthew Robert. "Molecular determinants of single channel conductance and ion selectivity in cationic Cys-loop receptor channels." Thesis, University of Dundee, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510623.

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29

Sunderman, Elizabeth R. "Single-channel kinetic analysis of the allosteric transition of rod cyclic nucleotide-gated channels /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/10526.

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30

Richards, Ryan. "Molecular and structural determinants that contribute to channel function and gating in channelrhodopsin-2." Digital WPI, 2016. https://digitalcommons.wpi.edu/etd-dissertations/481.

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The green algae Chlamydomonas reinhardtii senses light through two photosensory proteins, channelrhodopsin-1 (ChR1) and channelrhodopsin-2 (ChR2). The initial discovery of these two photoreceptors introduced a new class of light-gated ion channels. ChR2 is an inwardly-rectified ion channel that is selective for cations of multiple valencies. Similar to microbial-rhodopsin ion pumps, ChR2 has a seven transmembrane domain motif that binds the chromophore all-trans retinal through a protonated Schiff base linkage. Physiologically, ChR2 functions to depolarize the membrane which initiates a si

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31

Englund, Ulrika. "The role of ion channels and intracellular metal ions in apoptosis of Xenopus oocytes." Doctoral thesis, Linköpings universitet, Avdelningen för cellbiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-111045.

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Apoptosis is one type of programmed cell death, important during tissue development and to maintain the tissue homeostasis. Apoptosis comprises a complex network of internal signaling pathways, and an important part of this signaling network is the action of voltage‐gated ion channels. The aim of this thesis was to explore the role of ion channels and the role of intracellular metal ions during apoptosis in Xenopus laevis oocytes. The reasons for using these oocytes are that they are large, robust, easy to handle, and easy to study electrophysiologically. Apoptosis was induced either chemicall

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32

Bush, Elizabeth Rosina. "Molecular biology and expression of some ligand-gated ion channels from the nematodes Ascaris suum and Caenorhabditis elegans." Thesis, University of Southampton, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246225.

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33

Kirk, Kirsty-Anne. "The expression of potential molecular candidates for chloride ion channels in primary human granulocytes and granulocytic cell lines." Thesis, University of East Anglia, 2014. https://ueaeprints.uea.ac.uk/50544/.

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Introduction and hypothesis: The project aims to identify potential candidates for chloride (Cl-) ion channels in granulocytes, and granulocytic cell lines. It is hypothesised that Cl- ion channels, in particular hBest1, are implicated in the role of granulocytes in response to inflammation. Methodology: Two main methodologies were used; laboratory techniques and systematic review. Laboratory techniques included RT-PCR, flow cytometry and western blot analysis to characterise the expression of hANO1, hBest1 and hCLCA1 as potential chloride ion channels in granulocytes and granulocytic cell lin

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34

Jiang, Ruotian. "Molecular modus operandi of ligand-gated ion channels : Studies of trimeric P2X receptors and pentameric GABA A receptors." Strasbourg, 2011. http://www.theses.fr/2011STRA6086.

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Le principal objectif de cette thèse a été d’utiliser divers outils chimiques et biologiques afin de mieux décortiquer le mécanisme d’action au niveau moléculaire de deux membres des récepteurs appartenant à deux superfamilles différentes des récepteur canaux activés par les ligands: les récepteurs P2XRs et GABAARs. Le récepteur P2XR est un canal ionique sélectif aux cations activé par fixation de l'ATP extracellulaire. Mon objectif a été d’étudier les mécanismes moléculaires pour la liaison de l’ATP et l'ouverture rapide d’un canal ionique suite à la fixation de l’ATP. En utilisant l’approche

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35

Martin, Nicolas. "Allosteric modulation of pentameric ligand gated ion channels : from the jiggling of atoms to neuropharmacological strategies." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAF079/document.

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Les récepteurs pentamériques canaux (pLGICs) sont des récepteurs neuronaux impliqués dans la neurotransmission rapide et qui comprennent les récepteurs suivants : nAchR, GABAR, GlyR or 5HT3R. Lorsqu’ils ne fonctionnent pas correctement ils sont impliqués dans des pathologies comme Alzheimer ou Parkinson. Dans cette étude, nous avons réalisé des simulations de dynamique moléculaire d’un homologue procaryote des pLGICs. Grâce à l’analyse de 2.5 us de simulation nous avons pu capturer la fermeture complète dudit récepteur et décrire un mécanisme de gating. Ce mécanisme en deux étapes, 1) twisting

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36

Crozier, Paul S. "Slab-geometry molecular dynamics simulations : development and application to calculation of activity coefficients, interfacial electrochemistry, and ion channel transport /." Diss., CLICK HERE for online access:, 2001. http://contentdm.lib.byu.edu/ETD/image/etd15.pdf.

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37

Österberg, Fredrik. "Exploring Ligand Binding in HIV-1 Protease and K+ Channels Using Computational Methods." Doctoral thesis, Uppsala universitet, Strukturell molekylärbiologi, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6167.

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Understanding protein-ligand interactions is highly important in drug development. In the present work the objective is to comprehend the link between structure and function using molecular modelling. Specifically, this thesis has been focused on implementation of receptor flexibility in molecular docking and studying structure-activity relationships of potassium ion channels and their blockers. In ligand docking simulations protein motion and heterogeneity of structural waters are approximated using an ensemble of protein structures. Four methods of combining multiple target structures within

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38

Pirri, Jennifer K. "The Role of Ion Channels in Coordinating Neural Circuit Activity in Caenorhabditis elegans: A Dissertation." eScholarship@UMMS, 2013. http://escholarship.umassmed.edu/gsbs_diss/662.

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Despite the current understanding that sensorimotor circuits function through the action of transmitters and modulators, we have a limited understanding of how the nervous system directs the flow of information necessary to orchestrate complex behaviors. In this dissertation, I aimed to uncover how the nervous system coordinates these behaviors using the escape response of the soil nematode, Caenorhabditis elegans, as a paradigm. C. elegans exhibits a robust escape behavior in response to touch. The worm typically moves forward in a sinusoidal pattern, which is accompanied by exploratory head

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39

Kaprielian, Roger. "Molecular and cellular mechanisms associated with cardiac hypertrophy following myocardial infarction in rats, studies on ion channels and intracellular calcium." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0024/NQ49955.pdf.

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40

Newton, Hannah S. "Potassium channels and adenosine signaling in T cells of head and neck cancer patients." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1603713656776019.

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41

Boukharta, Lars. "Computational Modelling of Ligand Complexes with G-Protein Coupled Receptors, Ion Channels and Enzymes." Doctoral thesis, Uppsala universitet, Beräknings- och systembiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-212103.

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Accurate predictions of binding free energies from computer simulations are an invaluable resource for understanding biochemical processes and drug action. The primary aim of the work described in the thesis was to predict and understand ligand binding to several proteins of major pharmaceutical importance using computational methods. We report a computational strategy to quantitatively predict the effects of alanine scanning and ligand modifications based on molecular dynamics free energy simulations. A smooth stepwise scheme for free energy perturbation calculations is derived and applied to

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42

Moomaw, Andrea Sue. "Structure-Function Studies of the CorA Magnesium Channel." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1295621689.

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43

Idikuda, Vinaykumar. "REGULATION OF HCN CHANNEL FUNCTION BY DIRECT cAMP BINDING AND SINGLET OXYGEN." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5455.

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Hyperpolarization-activated, cyclic-nucleotide gated ion channels (HCN channels) are activated by membrane hyperpolarization and modulated by cyclic nucleotides. HCN channels are important to maintain the resting membrane potential and input resistance in neurons and have important physiological functions in the brain and heart. Four mammalian HCN isoforms, HCN1-4, and the isoform cloned from sea urchin, spHCN, have been extensively studied. Among these, only spHCN channel shows a voltage dependent inactivation. Previous studies have shown that the ligand binding in mHCN2 channel is activity d

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44

Carstens, Johanna J. "Identification of the modulators of cardiac ion channel function." Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/2163.

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Thesis (MScMedSc (Biomedical Sciences. Molecular Biology and Human Genetics))--University of Stellenbosch, 2009.<br>The human ether-à-go-go-related gene (HERG) encodes the protein underlying the cardiac potassium current IKr. Mutations in HERG may produce defective channels and cause Long QT Syndrome (LQTS), a cardiac disease affecting 1 in 2500 people. The disease is characterised by a prolonged QT interval on a surface electrocardiogram and has a symptomatic variability of sudden cardiac death in childhood to asymptomatic longevity. We hypothesised that genetic variation in the proteins

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45

Hanson, Sonya M. "Structural, biochemical and computational studies of TRP channel transmembrane domain modularity." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:328269a9-11c0-4d5b-9cb7-d7433cf4d6c4.

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Transient receptor potential (TRP) channels are expressed throughout the central nervous system and have a unique ability to detect a wide range of stimuli including changes in voltage, temperature, pH, lipid environment, small molecule agonists, and mechanical stress. While it is known that TRP channels contain the same six transmembrane helix (S1-S6), tetrameric architecture as voltage-gated channels, the degree to which functional and structural analogies are relevant remains poorly understood. This thesis describes a multidisciplinary approach toward understanding the structure and functio

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46

Cosseddu, Salvatore M. "Structure and dynamics of protein in the permeation and gating of potassium ion channels : identifying molecular determinants and developing coarse-grained approaches." Thesis, University of Warwick, 2013. http://wrap.warwick.ac.uk/62117/.

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Ion channels are transmembrane proteins which allow small ions to flow across the membrane downhill along the electrochemical gradient, with high effciency and selectivity over the different ion species, and which play crucial roles in a wide range of vital physiological functions. Research on the channels selective for potassium ions have attracted a great deal of attention over the past decade. This is because of the availability of three dimensional microscopical structures and because they provide a paradigm for the study of the complex superposition of the permeation of the ions and struc

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47

Gutheim, Sabina. "Characterization of Alcohol Modulation of a Pentameric Ligand-gated Ion Channel with Electrophysiology and Molecular Dynamics Simulations." Thesis, KTH, Tillämpad fysik, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-296530.

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Pentameric ligand-gated ion channels (pLGICs) are membrane receptors that play a crucial role in every living organism. The pLGIC protein structure forms a pore through the membrane of a cell that can let specific ions pass through, upon activation by endogenous agonists. pLGICs are allosterically modulated by ligands binding at allosteric sites, that either stabilize a certain conformation or change the binding affinity of the endogenous agonist. However, much remains unknown about the exact way in which these modulators bind to and affect pLGICs. An increased understanding could help in the

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Köpfer, David Alexander [Verfasser], Bert de [Akademischer Betreuer] Groot, and Ralf [Akademischer Betreuer] Ficner. "Ion Conductance Through Potassium Channels : Studied by Molecular Dynamics Simulations / David Alexander Köpfer. Gutachter: Bert de Groot ; Ralf Ficner. Betreuer: Bert de Groot." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2015. http://d-nb.info/107709678X/34.

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Makarewich, Catherine Anne. "MICRODOMAIN BASED CALCIUM INFLUX PATHWAYS THAT REGULATE PATHOLOGICAL CARDIAC HYPERTROPHY AND CONTRACTILITY." Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/266828.

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Molecular and Cellular Physiology<br>Ph.D.<br>Pathological cardiac stressors, including persistent hypertension or damage from ischemic heart disease, induce a chronic demand for enhanced contractile performance of the heart. The cytosolic calcium (Ca2+) transient that regulates myocyte contraction must be persistently increased in disease states in order to maintain cardiac output to sustain the metabolic requirements of the body. Associated with this enhanced intracellular Ca2+ ([Ca2+]i) state is pathological cardiac myocyte hypertrophy, which results in large part from the activation of Ca2

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Mahajan, Rahul. "Gβγ acts at an inter-subunit cleft to activate GIRK1 channels". VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/3307.

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Heterotrimeric guanine nucleotide-binding proteins (G-proteins) consist of an alpha subunit (Gα) and the dimeric beta-gamma subunit (Gβγ). The first example of direct cell signaling by Gβγ was the discovery of its role in activating G-protein regulated inwardly rectifying K+ (GIRK) channels which underlie the acetylcholine-induced K+ current responsible for vagal inhibition of heart rate. Published crystal structures have provided important insights into the structures of the G-protein subunits and GIRK channels separately, but co-crystals of the channel and Gβγ together remain elusive and no

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