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1
Männikkö, Roope. "Voltage sensor movements in shaker and HCN channels /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-739-8.
Testo completo
2
Donini, Oreola Anna Teresa. "Ion channels in motion, developing computational approaches to dynamic ion channel modeling". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ35957.pdf.
Testo completo
3
Hoyles, Matthew, e Matthew Hoyles@anu edu au. "Computer Simulation of Biological Ion Channels". The Australian National University. Theoretical Physics, 2000. http://thesis.anu.edu.au./public/adt-ANU20010702.135814.
Testo completoAbstract (sommario):
This thesis describes a project in which algorithms are developed for the rapid and accurate solution of Poisson's equation in the presence of a dielectric boundary and multiple point charges. These algorithms are then used to perform Brownian dynamics simulations on realistic models of biological ion channels. An iterative method of solution, in which the dielectric boundary is tiled with variable sized surface charge sectors, provides the flexibility to deal with arbitrarily shaped boundaries, but is too slow to perform Brownian dynamics. An analytical solution is derived, which is faster and more accurate, but only works for a toroidal boundary. Finally, a method is developed of pre-calculating solutions to Poisson's equation and storing them in tables. The solution for a particular configuration of ions in the channel can then be assembled by interpolation from the tables and application of the principle of superposition. This algorithm combines the flexibility of the iterative method with greater speed even than the analytical method, and is fast enough that channel conductance can be predicted. The results of simulations for a model single-ion channel, based on the acetylcholine receptor channel, show that the narrow pore through the low dielectric strength medium of the protein creates an energy barrier which restricts the permeation of ions. They further show that this barrier can be removed by dipoles in the neck of the channel, but that the barrier is not removed by shielding by counter-ions. The results of simulations for a model multi-ion channel, based on a bacterial potassium channel, show that the model channel has conductance characteristics similar to those of real potassium channels. Ions appear to move through the model multi-ion channel via rapid transitions between a series of semi-stable states. This observation suggests a possible physical basis for the reaction rate theory of channel conductance, and opens up an avenue for future research.
4
Craven, Kimberley Beth. "Structural rearrangements during gating in cyclic nucleotide-modulated channels /". Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/10654.
Testo completo
5
Breed, Jason. "Molecular modelling of ion channels". Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308690.
Testo completo
6
MacKenzie, Amanda Barbara. "Ion channels in human platelets". Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627035.
Testo completo
7
Ball, Sue. "Stochastic models of ion channels". Thesis, University of Nottingham, 2001. http://eprints.nottingham.ac.uk/11277/.
Testo completoAbstract (sommario):
This thesis is concerned with models and inference for single ion channels. Molecular modelling studies are used as the basis for biologically realistic, large state-space gating models of the nicotinic acetylcholine receptor which enable single-channel kinetic behaviour to be characterized in terms of a small number of free parameters. A model is formulated which incorporates known structural information concerning pentameric subunit composition, interactions between neighbouring subunits and knowledge of the behaviour of agonist binding sites within the receptor-channel proteins. Expressions are derived for various channel properties and results are illustrated using numerical examples. The model is adapted and extended to demonstrate how properties of the calcium ion-activated potassium ion channel may be modelled. A two-state stochastic model for ion channels which incorporates time interval omission is examined. Two new methods for overcoming a non-identifiability problem induced by time interval omission are introduced and simulation studies are presented in support of these methods. A framework is presented for analysing the asymptotic behaviour of the method-of-moments estimators of the mean lengths of open and closed sojourns. This framework is used to clarify the origin of the non-identifiability and to construct confidence sets for the mean sojourn lengths. A conjecture concerning the number of solutions of the moment estimating equations is proved.
8
Swallow, Isabella Diane. "Probes for bacterial ion channels". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:d42d13dd-dd0c-451b-bd00-e06f84350335.
Testo completoAbstract (sommario):
Using three complementary approaches, this work sought to tackle the widespread problem of antibiotic resistance. To circumvent the resistance mechanisms developed by bacteria, it is necessary to establish drug candidates that act on novel therapeutic targets, such as the ion channels used by bacteria to modulate homeostasis. Examples include the potassium efflux channel, Kef, and the mechanosensitive channel of small conductance, MscS, which are not found in humans. How these targets function must be well understood before drug candidates can be developed, as such, their identification and investigation is often accompanied by the evolution of the analytical techniques used to study them. Membrane protein mass spectrometry is one technique showing potential in the study of ion channels. However, spectra can be clouded by the detergents used to solubilise ion channels from their native membranes. Undertaken herein was the synthesis of some fluorescent glycolipid detergents, which it was hypothesised could be encouraged to dissociate from ion channels via laser-induced excitation within the gas phase of a mass spectrometer, thereby improving the clarity with which spectra can be obtained. For Kef, an unconfirmed mechanism of action had previously been proposed. To explore the suggestion that sterically-demanding central residues are important for channel activation, solid phase peptide synthesis was used to isolate three tripeptide analogues of N-ethylsuccinimido glutathione, a known activator with a high affinity for Kef. A competition fluorescence assay suggested these tripeptides bound to Kef with an affinity lower than predicted, allowing the conclusion that a more detailed assessment of the steric bulk required for activation was necessary before a mechanism of action could be confirmed. Lysophosphatidylcholine has been shown to activate MscS, although it is not known how. Affinity chromatography between MscS and lysophosphatidylcholine was proposed as a means by which specific binding interactions could be investigated. For this technique an amino-derivative of lysophosphatidylcholine was necessary and its challenging synthesis is also detailed herein.
9
Matulef, Kimberly Irene. "Cysteine-scanning mutagenesis of the ligand-binding domain of cyclic nucleotide-gated channels /". Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/5032.
Testo completo
10
Zhang, Hongling. "Sigma Receptors Modulation of Voltage-gated Ion Channels in Rat Autonomic Neurons". [Tampa, Fla.] : University of South Florida, 2005. http://purl.fcla.edu/fcla/etd/SFE0001183.
Testo completo
11
Khatchadourian, Rafael Aharon. "Characterization of histidine-tagged NaChBac ion channels". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116024.
Testo completoAbstract (sommario):
Imaging tools in cellular and molecular biology have long relied on organic fluorophores to observe microorganisms or various cell constituents. The advent of semiconductor nanoparticles known as quantum dots (QDs) has offered the possibility to use this new class of fluorescent probes with very advantageous optical properties in cell biology. The imaging of transmembrane potential and ionic currents is of significant importance for monitoring the activity of the cell. It remains possible with relatively complicated instruments and methods such as patch clamping. A complementary approach to view the dynamics of ion channels with modern and efficient fluorophores is therefore of great interest to the field of biology in general.We developed a construct based on the FRET signal between QDs and organic fluorescent dyes to monitor the conformational changes of voltage gated sodium channels. The amino acid histidine was used as a "landing platform" for QDs and the bacterial sodium channel NaChBac was chosen for testing. This study focused on the preliminary steps of the project and aimed to characterize the electrophysiological behavior of the histidine-tagged channel. The whole-cell configuration of patch clamping was the tool we used to understand the differences between the wild-type and the histidine-tagged variants of the channels. We also explore the possibility to land QDs on the histidine tag.
12
Giorgetti, Alejandro. "Structural predictions of HCN/CNG ion channels: Insights on channels' gating". Doctoral thesis, SISSA, 2004. http://hdl.handle.net/20.500.11767/4655.
Testo completoAbstract (sommario):
Evolution built a membrane around the earliest forms of life in order to isolate them from the external environment. The cell membrane is constituted by two layers of phospholipids, which are molecules having a polar head and non-polar tails. Two films of these molecules are assembled together by hydrophobic forces building a very stable lipid bilayer.
Inserted in this amphiphilic environments are membrane proteins, which have both hydrophobic and hydrophilic regions on their surface. In highly evolved and specified cells this class of proteins carries out a variety of different activities essential for the cell and organism life, like the antibody recognition in lymphocytes and the nervous pulse transmission in neurons.
Although the presence of the membrane helps cells to retain vital ingredients, it prevents the access to necessary ionized substrates and ions, because the hydrophobic core is a high free energy barrier in the diffusion of charged molecules.
Membrane spanning pores are a common feature to ionic channels (Hille, 2001;Chang et al., 1998), and they are presents in different classes of other biological transporter proteins like bacterial porins and aquaporins.
Special membrane proteins, the ionic channels, form holes through the cell membrane, providing a feasible path for ion exchanges.
13
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.
Testo completoAbstract (sommario):
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 follow-up study, we found that the energetic cost of translocating this 310-helix conformation was significantly lower than in the original conformation. Thirdly, collaborators of ours identified new molecular constraints for different states along the gating pathway. We used those to build new protein models that were evaluated by simulations. All these results point to a gating mechanism where the S4 helix undergoes a secondary structure transformation during gating. These simulations also provide information about how the protein interacts with the surrounding membrane. In particular, we found that lipid molecules close to the protein diffuse together with it, forming a large dynamic lipid-protein cluster. This has important consequences for the understanding of protein-membrane interactions and for the theories of lateral diffusion of membrane proteins. Further, simulations of the simple ion channel antiamoebin were performed where different molecular models of the channel were evaluated by calculating ion conduction rates, which were compared to experimentally measured values. One of the models had a conductance consistent with the experimental data and was proposed to represent the biological active state of the channel. Finally, the underlying methods for simulating molecular systems were probed by implementing the CHARMM force field into the GROMACS simulation package. The implementation was verified and specific GROMACS-features were combined with CHARMM and evaluated on long timescales. The CHARMM interaction potential was found to sample relevant protein conformations indifferently of the model of solvent used.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.
14
Corry, Ben Alexander, e ben corry@anu edu au. "Simulation Studies of Biological Ion Channels". The Australian National University. Research School of Physical Sciences and Engineering, 2003. http://thesis.anu.edu.au./public/adt-ANU20030423.162927.
Testo completoAbstract (sommario):
Biological ion channels are responsible for, and regulate the
communication system in the body. In this thesis I develop, test and
apply theoretical models of ion channels, that can relate their
structure to their functional properties. Brownian dynamics
simulations are introduced, in which the motions of individual ions
are simulated as they move through the channel and in baths attached
to each end. The techniques for setting boundary conditions which
maintain ion concentrations in the baths and provide a driving
potential are tested. Provided the bath size is large enough, all
boundary conditions studied yield the same results.
¶
Continuum theories of electrolytes have previously been used to study
ion permeation. However, I show that these continuum models do not
accurately reproduce the physics taking place inside ion channels by
directly comparing the results of both equilibrium Poisson-Boltzmann
theory, and non-equilibrium Poisson-Nernst-Planck theory to
simulations. In both cases spurious shielding effects are found to
cancel out forces that play an important role in ion permeation. In
particular, the `reaction field' created by the ion entering the
narrow channel is underestimated. Attempts to correct these problems
by adding extra force terms to account for this reaction field also
fail.
¶
A model of the L-type calcium channel is presented and studied using
Brownian dynamics simulations and electrostatic calculations. The
mechanisms of permeation and selectivity are explained as the result
of simple electrostatic interactions between ions and the fixed
charges in the protein. The complex conductance properties of the
channel, including the current-voltage and current-concentration
relationships, the anomalous mole fraction behaviour between sodium
and calcium ions, the attenuation of calcium currents by monovalent
ions and the effects of mutating glutamate residues, are all
reproduced.
¶
Finally, the simulation and electrostatic calculation methods are used
to study the gramicidin A channel. It is found that the continuum
electrostatic calculations break down in this narrow channel, as the
concept of applying a uniform dielectric constant is not accurate in
this situation. Thus, the permeation properties of the channel are
examined using Brownian dynamics simulations without electrostatic
calculations. Future applications and improvements of the Brownian
dynamics simulation technique are also described.
15
Vijayan, Ranjit. "Computational Studies of Ligand_Gated Ion Channels". Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504618.
Testo completo
16
Stanton, Craig. "Mechanosensitive ion channels in osteoarthritis pain". Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121326.
Testo completoAbstract (sommario):
Osteoarthritis (OA) is a debilitating disease affecting nearly 5 million of Canadians, with aneconomic impact of over $30 billion each year in direct and indirect costs. Pain is the prominent symptom of OA, yet its underlying mechanisms are not completely understood, leading to a lack of effective pain therapies. OA pain is manifested by a hypersensitivity to mechanical stimuli such as joint movement or palpation. Although the mechanical sensitization of pain-sensing nerve fibers, known as nociceptors, innervating the joint has been documented, the molecular and cellular mechanisms underlying this sensitization are currently unknown. The peripheral terminals of nociceptors express mechanosensitive ion channels (MSCs) that convert mechanical stimuli into depolarizing potentials. Our central hypothesis is that the sensitization of nociceptors to mechanical stimuli in OA can be explained by changes in the properties of these MSCs, whereby their activation threshold is reduced during the disease. Using the monoiodoacetate model of OA in mice, we demonstrate that mice develop chronic mechanical allodynia. Furthermore, cell–attached electrophysiological recordings of nociceptors isolated from OA mice indicate an increase in the current elicited by mechanical stimuli, as well as a reduced activation threshold of MSCs, when compared to naïve mice. An understanding of the molecular bases for these changes is presently impossible because the identity of the genes encoding MSCs isunknown. Interestingly, in a previous screen for MSC candidates, we identified five transmembrane proteins of unknown function (TMEMs). Our results indicate these candidates are expressed in sensory neurons and the mRNA of three of them is increased in OA. When expressed in COS-7 cells, two of these candidates, TMEM5B and TMEM1, caused an increase and decrease in cellular mechanosensitivity. This project will lead to a better understanding of the molecular mechanisms underlying arthritis pain.L'ostéoarthrite (OA) est une maladie débilitante affectant près de 5 millions de Canadiens et ayant un impact économique de plus de 30 milliards de dollars en coûts directs et indirects. Bienque le symptôme principal de l'OA est la douleur, les mécanismes qui en sont responsables ne sont pas compris, et par conséquent, les thérapies effectives contre la douleur sont manquantes. La douleur causée par l'OA est manifestée par une hypersensibilité aux stimuli mécaniques tels le mouvement des jointures ou la palpation. Bien que la sensibilisation mécanique des fibres nerveuses qui détectent la douleur (nocicepteurs) innervant la jointure ait été documentée, les mécanismes moléculaires et cellulaires de base de la sensibilisation ne sont pas compris. Les terminaisons périphériques des nocicepteurs expriment des canaux ioniques mécanosensibles (MSCs) responsables de la conversion des stimuli mécaniques en potentiels dépolarisants. Notrehypothèse centrale est que durant l'OA, la sensibilisation des nocicepteurs aux stimulimécaniques peut être attribuée aux changements des propriétés de base des MSCs, où leur seuil d'activation est réduit lors de la maladie. Nous démontrons, en utilisant le modèle de monoiodoacetate de l'OA chez la souris, que cette dernière développe une allodynie mécaniquechronique. De plus, les enregistrements électrophysiologiques en configuration cellule-attachée faites à partir des nociceptors isolés des souris OA indiquent une augmentation du courant élicitépar les stimuli mécaniques, ainsi qu'une réduction dans le seuil d'activation des MSCs encomparaison aux souris naïves. Une compréhension de la base moléculaire de ces changements est présentement impossible car l'identité des gènes qui encodent les MSCs n'est pas connue. Dans des expériences antérieures, au cours desquelles nous avons fait un criblage différentiel afin d'identifier des candidats de MSC, nous avons identifié cinq protéines transmembranaires de fonctions inconnues (TMEMs). Nos résultats indiquent que ces candidats sont exprimés dans les neurones sensoriels et que l'ARNm de trois de ces derniers augmente durant l'OA. Lorsqu'exprimés dans les cellules COS-7, deux des candidats (TMEM5B et TMEM1) ont causé une augmentation et une diminution de la mécanosensibilité cellulaire. Ce projet nous donnera une meilleure compréhension des mécanismes moléculaires de base de la douleur arthritique.
17
Knock, Gregory Alan. "Ion channels in the human myometrium". Thesis, King's College London (University of London), 1999. https://kclpure.kcl.ac.uk/portal/en/theses/ion-channels-in-the-human-myometrium(7d934328-7950-4389-8315-0d886bcd65aa).html.
Testo completo
18
Mellor, Ian R. "The biophysics of peptide ion channels". Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335759.
Testo completo
19
Martin, Richard John. "Veterinary pharmacology, ion-channels and anthelmintics". Thesis, University of Edinburgh, 1997. http://hdl.handle.net/1842/30450.
Testo completoAbstract (sommario):
In this collection of papers modes of action of anthelmintic and anaesthetic drugs used in Veterinary Practice are investigated using electrophysiological techniques. New preparations and analytical techniques for investigation are described along with properties of ion-channel target sites. The pharmacology of piperazine, levamisole, pyrantel, morantel, oxtantel, avermectins, cyclic depsipeptides, ketamine, metomidate, alphaxalone and xylazine are studied. This information is reviewed in formats suitable for graduate and undergraduate study. Two-micropipette current-clamp and voltage-clamp techniques for recording effects of GABA agonists and antagonists on nematode muscle are developed using Ascaris suum. Piperazine, an anthelmintic, is shown to act as a GABA agonist of low potency and, like GABA, to mediate an increase in Cl conductance by an action on extrasynaptic receptors. Diethylcarbamazine, a piperazine derivative, did not act as a GABA agonist but blocked a voltage-activated K current. The agonist profile of the Ascaris GABA receptor was similar to vertebrate GABAA receptors but the antagonist profile was very different, indicating the presence of a distinctive type of receptor (GABAN). Novel arylaminopyridazine derivatives were synthesised and tested as competitive antagonists on the GABAN receptor. The KB for NCS 281-93, was 4.7 μM. A preparation suitable for patch-clamp studies was developed and GABA receptors activated by GABA and piperazine. Both agonists activated channels with a mean single-channel conductance of 22 pS but GABA mean open-times were longer (32ms) than those of piperazine (14 ms). The effects of ivermectin on muscle GABA receptors in Ascaris and on 19 pS Cl channels were observed using cell-attached and isolated inside-out patches. Ivermectin locked open the small Cl channels when applied to the outside membrane. A novel fluorescent and active bodily ivermectin analogue was synthesised and the movement of the probe followed in vesicle membranes using the FRAP (fluorescence recovery after photobleaching) technique. Quenching experiments showed that the ivermectin probe did not move through the cell membrane in the time scale of the experiment (30 min). A novel two-microelectrode current-clamp preparation of the Ascaris pharynx was used to show that an ivermectin analogue potentiated a glutamate gated Cl channel at low concentrations and produced an increase in the Cl conductance at a higher concentration. The actions of potent and novel potential anthelmintic cyclic depsipeptides were investigated using conventional parasitological techniques and the mode of action investigated in Ascaris muscle using current-clamp. It was found that these compounds did not act directly as a GABA agonist or acetylcholine antagonist. The actions of the anthelmintic praziquantel are reviewed and a tegumental preparation of Schistosoma mansoni developed for single-channel recording.
20
Casula, Maria Anna. "Novel ion channels in neurogenic pain". Thesis, Imperial College London, 2009. http://hdl.handle.net/10044/1/7568.
Testo completoAbstract (sommario):
It was hypothesized that modulation of expression of sensory ion channels and receptors by disease or trauma results in spontaneous or ectopic discharges, mediated mainly via sodium channels, and hypersensitivity of nerve terminals, mainly via receptors of the TRP family and the purinoceptor P2X7. Sensory neurons and characterised tissues were studied, using immunocytochemistry, in common clinical chronic pain states. The key novel findings are: (1) TRPVI is the most selective pain target of the TRP family - it is abundant in pelvic afferents, and TRPV1-positive fibres are increasd in vulvodynia; TRPV1 blockade may be particularly effective in visceral hypersensitivity. Studies in cultured human sensory neurons demonstrate that Nerve Growth Factor and other neurotrophic factors may regulate the increased expression of TRPV1; (2) P2X₇ receptor levels were increased in painful injured human nerves. In mice with a disrupted P2X₇ gene, inflammatory and neuropathic hyperalgesia was completely absent. P2X₇ receptor appears pivotal in chronic inflammatory and neuropathic sensitization to noxious stimuli, and (3) there is an up-regulation of the β3 subunit which modulates sodium channel activation, in human peripheral nerves after injury, and thus represents a novel selective target for spontaneous pain. In conclusion, multiple molecular mechanisms are thus involved in pain states, and strategies which combine drugs aimed at these targets may be necessary for improved clinical efficacy.
21
Gay, Robert Adam. "Regulation of guard cell ion channels". Thesis, University of Glasgow, 2004. http://theses.gla.ac.uk/30730/.
Testo completoAbstract (sommario):
Stomatal guard cells regulate the stomatal aperture to allow gas exchange whilst minimising water loss from the plant. Stomatal movements are driven by changes in the ion transport across the various membrane systems through ion channels and pumps. Complex signaling events are involved in the regulation of ion channels during stomatal movements. Whilst considerable progress has been made in the understanding of ion transport processes, some questions still remain. Regulation of guard cell ion channels by the gaseous free radical nitric oxide, (NO), was investigated using electrophysiological and Ca2+ imaging techniques. Treatment of intact guard cells with NO donor and scavenger compounds revealed that NO modulates the Ca2+-sensitive inward rectifier K+ channel (IK,in) and anion channel (Ici) by enhancing Ca2+ release from internal stores. The NO-enhanced Ca2+ release is via a cGMP / cADPR pathway, thus showing similarities with animal NO signalling. Furthermore, abscisic acid (ABA) regulation of Ik,in and Ici is abolished by the nitric oxide scavenger compounds, placing NO as a key component of ABA-mediated ion channel regulation. NO regulation of IK,in and Ici was abolished by the broad range protein kinase inhibitor staurosporine, which blocked the NO enhancement of Ca2+ release from internal stores. Stomatal movements also involve changes in volume and surface area, which must be accommodated by delivery and retrieval of membrane material. Fusion and fission of membrane material requires protein machinery called SNARE proteins, which include syntaxins. The discovery of a syntaxin, NtSyr1, which is involved in hormonal control of ion channel gating, along with patch clamp measurements of cell surface area, raised the possibility of interaction between membrane traffic and ion channel regulation. To explore this possibility further, experiments were carried out using pharmacological tools and transgenic plants expressing the cytosolic portion (SP2) of NtSyr1 under the control of a dexamethasone inducible promoter (dexSP2-14 plants). Experiments with the membrane traffic inhibitor brefeldin A (BFA) and the actin antagonist latrunculin B (LATB), showed coupling of lK,in channel activity with membrane traffic and both IK,in and the outward rectifier K+ channel (IK,out) with actin filaments. Furthermore, analysis of voltage evoked Ca2+ signals in dexSP2-14 plants showed that voltage evoked Ca2+ signals were altered by SP2 protein expression. These data, along with stomatal aperture measurements, suggest a coupling of membrane trafficking and cell volume regulation processes with ion channel control.
22
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.
Testo completo
23
Song, Hyun Deok. "Computer Simulation Studies of Ion Channels at High Temperatures". University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1328890332.
Testo completo
24
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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25
Zubcevic, Lejla. "Structure and function of bacterial ion channels". Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:4585a56f-f6cd-44cb-845f-a3ac397fcf38.
Testo completoAbstract (sommario):
KirBac channels are prokaryotic homologs of eukaryotic inwardly-rectifying potassium channels, which have served as models for gaining insight into the structure of eukaryotic channels. This thesis focuses on the structure-function relationship in these channels. The first part of this study concerns a novel KirBac channel, KirBac9.2, which contains a unique amino acid sequence in the place of the canonical GYG selectivity filter. Although expressed and purified in a stable and functional form, the protein did not form well-diffracting crystals. Functional studies suggest that KirBac9.2 is non-selective for monovalent cations and a random mutagenesis screen identified a number of activatory mutants in the cytoplasmic domains of the channel. A full electrophysiological investigation of KirBac9.2 channel function is beyond the scope of this study. However, initial studies suggest that it is possible to record currents from KirBac9.2 channels reconstituted into lipid bilayers. The second part of this thesis investigates KirBac3.1, which is a classical KirBac channel containing the consensus GYG sequence for potassium selectivity. Five high resolution structures of a mutant channel are reported, which suggest a new feature in the gating mechanism of KirBac3.1 where a rotation of the cytoplasmic domains is linked to a change in the electrostatic environment of the cytoplasmic cavity. In addition, a functional study of the KirBac3.1 showed that the channel is highly pH sensitive.
26
Zeng, Shangyou. "Spatial distribution and function of ion channels on neural axon". Ohio : Ohio University, 2005. http://www.ohiolink.edu/etd/view.cgi?ohiou1113855357.
Testo completo
27
Fisher, J. A. "Understanding the regulation of ion flow through P2X receptor ion channels". Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599054.
Testo completoAbstract (sommario):
The cytosolic C-terminal tails of P2X2 subunits were labelled with either cyan or yellow fluorescent proteins (CFP and YFP, respectively). Co-expression of these subunits in human embryonic kidney cells resulted in functional P2X receptors at the plasma membrane that underwent FRET with an efficiency of 34 %. Time-resolved measures of FRET suggested that conformational changes in the C-terminal tails of P2X2-C/P2X2Y receptors were correlated with agonist and time dependent increases in permeability. Similar FRET based measures, suggestive of conformational changes, were not observed in the C-terminal tails of P2X receptors that did not show agonist and time dependent increases in permeability. Furthermore, tethering the P2X2 C-terminal tail prevented permeability changes and abolished conformational changes in the C-terminal tails. Cleavage of the tether restored both phenotypes. Previously generated and characterised α4 and β2 and P2X2 subunits were co-expressed in mammalian cells and shown to undergo cross-inhibition. FRET was used to show that, within ~ 100 nm of the plasma membrane, fluorophore labelled P2X2 and α4β2 nACh receptors were positioned within ~ 80 Å of each other. The FRET signal between these two receptors was greater when the β2 subunit of α4β2 nACh receptor was fluorophore labelled, rather than the α4 subunit, suggesting a preferential orientation for the interaction. This interaction was also measured in hippocampal neurons. In summary the data indicate that the C-terminal tails of P2X2 receptors undergo conformational changes associated with a specific functional property. In addition the C-terminal tails of P2X2 receptors undergo significant spatial interactions with β2 subunits in α4β2 nicotinic acetylcholine receptors. Overall, FRET appears to be a useful complementary approach to study P2X receptors.
28
Neff, Stephan. "Heavy-ion beam transport in plasma channels transport properties and channel stability /". [S.l. : s.n.], 2005. http://elib.tu-darmstadt.de/diss/000561.
Testo completo
29
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.
Testo completo
30
Zha, Huiyan, e 查慧艳. "Design, synthesis and characterization of synthetic ion transporters". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hdl.handle.net/10722/206532.
Testo completoAbstract (sommario):
In recent decades, small molecules have been widely applied to the generation of functional ion transporters. Major discoveries disclosed in this thesis include a self-assembled chloride-dependent potassium channel candidate, a physiological chloride and bicarbonate dual-transporter, and a series of efficient synthetic ion transporters.
In nature, K+ channels play an important role in Ca2+ signaling, volume regulation, secretion, proliferation, and migration. The extracellular K+ concentration (4 mM) is about 40 times lower than the intracellular K+ concentration (160 mM). The opening of K+ channels consequently generates an efflux of positive charge, which hyperpolarizes or repolarizes the cellular membrane. In this research, by using fluorescence assays, NMR and patch clamp experiments, compound ZHY-CM23 was found to self-assemble into a chloride-dependent K+ selective channel mediating K+ transport across lipid bilayers and cell membranes. In addition, the synthetic K+ channel formed by ZHY-CM23 was found to be capable of generating and modulating the membrane potential of liposomes and to significantly hyperpolarize the resting membrane potential of HEK 293 cells. This finding provides new insight into developing drugs for the treatment of severe human diseases caused by K+ channel malfunction, such as arrhythmia, neurological disorders and autoimmune diseases.
Cystic fibrosis is a chronic recessive disease resulting from the loss of function mutations in the gene encoding of the cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ABC family of membrane transporters. Recent findings reveal that restoring bicarbonate transport might be useful for the treatments of the underlying defect in cystic fibrosis. On the basis of fluorescence assays, NMR and short circuit current experiments, the small molecule ZHY-CM11 has been discovered to not only act as a bicarbonate transporter in lipid membranes, but also to induce chloride-dependent bicarbonate secretion in cultured calu-3 epithelia. It is a promising lead compound to be developed for the treatment of cystic fibrosis and other diseases related to chloride and bicarbonate transport defects.
Through structural modifications on the bioactive ion channels and the transporters ZHY-CM23 and ZHY-CM11, some valuable information on the structure-activity relationship has been obtained, and a series of potentially biologically applicable synthetic ion transporters have been discovered.published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy
31
Pardo, Pastor Carlos 1989. "Piezo ion channels in cancer cell mechanotransduction". Doctoral thesis, Universitat Pompeu Fabra, 2018. http://hdl.handle.net/10803/664209.
Testo completoAbstract (sommario):
The mechanical dependence of transformation and metastasis is an emerging field, but the role of mechanosensitive channels has been largely omitted. This thesis focuses on the roles played by the mechanosensitive ion channels Piezo1 and Piezo2 in the transduction of mechanical stimuli (confinement, adhesion, substrate rigidity, adhesive ligand concentration) by cancer cells.
In a first chapter, we show that confinement triggers Piezo1-mediated calcium entry. This activates phosphodiesterase 1, reducing cAMP levels and, consequently, PKARac1 activity, relieving Myosin II from its inhibition. We also find a parallel, direct activation of Myosin II by confinement. As a combined result, cells stiffen and optimize their adhesion-free migration mode, usually responsible for in vivo migration during metastatic invasion. Piezo1 knockdown supresses confinement-induced calcium entry and impairs the underlying circuitry in ovarian epithelial (CHO) or melanoma (A375) cells. As a result, siPiezo1 cells show reduced migratory capacity under confinement.
In the second chapter, we discover an essential role for Piezo2 as a transducer of environmental mechanical cues into RhoA activation to modulate the mechanobiological responses of MDA-MB-231-BrM2 brain metastatic breast cancer cells. Piezo2 knockdown disturbs stress fibre formation, adhesion orientation, force transmission and nuclear accumulation of the malignant co-transcriptional activator YAP, and this is phenocopied by extracellular calcium suppression. Promoting Actin polymerization with jasplakinolide or by over-expressing constitutively active forms of Rho or mDia1 restores stress fibres and nuclear YAP accumulation. In addition, Piezo2 knockdown disrupts several pro-metastatic functions: cell proliferation, migration, invadopodia formation, extracellular matrix degradation, and secretion of SERPINB2, a protein needed for protecting invasive cells from brain parenchymal defence mechanisms.
The works presented in this thesis unveil important roles for Piezo channels as a first line of mechanical input detectors in distinct cells. These discoveries are relevant for several fields, e.g. cancer research, and highlight the importance of ion channels as transducers of environmental stimuli.La dependència mecànica de la transformació i la metàstasi és un camp d’estudi / de recerca emergent, però el paper que hi juguen els canals iònics mecanosensibles s’ha omès fins ara. Aquesta tesi se centra en els rols dels canals Piezo1 i Piezo2 en la transducció d’estímuls mecànics per cèl·lules canceroses, com ara confinament, adhesió, rigidesa del substrat, concentració de lligands adhesius. En un primer capítol, mostrem que el confinament dispara l’entrada de calci per mitjà de Piezo1. Això activa la fosfodiesterasa 1, que redueix els nivells d’AMPc i, en conseqüència, l’activitat PKARac1, que deixen d’inhibir Miosina II. També trobem una activació paral·lela de Miosina II directament per confinament. Com a resultat final, les cèl·lules guanyen rigidesa i optimitzen el seu mode migratori independent d’adhesions, que és el preponderant in vivo durant la invasió metastàtica. Reduir els nivells de Piezo1 suprimeix l’entrada de calci induïda per confinament i desactiva el circuit subjacent en cèl·lules ovàriques epitelials (CHO) i de melanoma (A375). Això minva la capacitat migratòria de les cèl·lules siPiezo1. En un segon capítol, descobrim un rol essencial per a Piezo2 com a activador de RhoA en resposta a estímuls mecànics. Això modula les respostes mecanobiològiques de les cèl·lules MDA-MB-231-BrM2, de càncer de mama metastàtic a cervell. La reducció dels nivells de Piezo2 destorba la formació de fibres d’estrès, l’orientació de les adhesions, la transmissió de forces i l’acumulació nuclear del regulador transcripcional prometastàtic YAP. Suprimir el calci extracel·lular fenocòpia aquests resultats. Promoure la polimerització d’Actina amb jasplaquinolida o mer mitjà de la sobreexpressió de formes constitutivament actives de RhoA o mDia1 restableix les fibres d’estrès i l’acumulació nuclear de YAP. A més, la reducció de Piezo2 suspèn diverses funcions prometastàtiques: proliferació cel·lular, migració, formació d’invadopodis, degradació de la matriu extracel·lular i secreció de SERPINB2, una proteïna necessària per protegir les cèl·lules invasores dels mecanismes de defensa del parènquima cerebral. Els treballs presentats en aquesta tesi desvelen rols importants pels canals Piezo com a una primera línia de detectors d’estímuls mecànics en diferents tipus cel·lulars. Aquests descobriments són rellevants per a diversos àmbits, com ara la recerca en càncer, i remarquen la importància dels canals iònics com a transductors d’estímuls ambientals.
32
Steller, Laura Florentina. "Engineering of Light-Gated Artificial Ion Channels". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2007. http://nbn-resolving.de/urn:nbn:de:swb:14-1169805885137-06514.
Testo completoAbstract (sommario):
The goal of this project is the development of artificial ion channels that can be actuated by light and thus controlled efficiently. Our artificial system is composed of two regions: the gate and the body part. The gate part is based on light-responsive azo groups while the body part is formed by calix[4]resorcinarene. Key of controlling mechanism is the conformational change between cis and trans isomers, which is translated into movement of the gate. Light-gated artificial ion channels are aimed at eliminating of the stochastic mechanism of artificial ion channels. Such a reversible photocontrol should be a powerful tool for using artificial ion channels as the basis for the development of new pharmaceuticals and drug delivery systems, as photoswitches, and in the field of microfluidics.
33
Tester, Mark Alfred. "Studies of ion channels in Chara corallina". Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293901.
Testo completo
34
Ren, Yilei. "Mathematical Modelling of Voltage-Gated Ion Channels". Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523670.
Testo completo
35
Lewis, Rebecca. "The role of ion channels in chondrocytes". Thesis, University of Liverpool, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569652.
Testo completoAbstract (sommario):
Chondrocytes are the cells of articular cartilage responsible for the production and maintenance of their extracellular matrix (ECM). They exist in a unique environment of low partial pressures of oxygen, low pH and avascularity (Urban, 1994). The chondrocyte environment is also challenged by constant osmotic fluxes during osmolarity changes induced by joint loading. This thesis investigates the ion channels expressed by chondrocytes and examines the possible functions for these channels. Whole cell and single channel electrophysiological experiments identified chloride, sodium, potassium and non-selective cation conductances in isolated canine chondrocytes. Whole-cell current clamp measurements of membrane potential (Vm) showed that chondrocytes have very depolarised Vm compared to other cell types (in the range of -8 to -14mV, measured from bovine, ovine, equine and canine chondrocytes). Permeability experiments carried out in whole-cell voltage clamp mode determined that the non-selective cation current was selective for calcium over sodium and potassium at a level similar to that of the transient receptor potential vanilloid type five and six channels (TRPVS and 6). RT-PCR detected mRNA for TRPV4 and TRPVS channels. The effect of these channels on chondrocyte membrane potential (Vm) was determined using whole-cell current-clamp electrophysiology. Experiments with the selective TPRVS inhibitor econazole suggest that TRPVS is constitutively active and important for setting the depolarised Vm. Conversely, TRPV4 appeared to be inactive at rest and when activated by the selective agonist 4 a-phorbol 12,13-didecanoate indirectly caused an increase in potassium conductance and thus membrane hyperpolarisation. A low conductance sodium channel was also identified. Sensitivity to low concentrations of amiloride and benzamil indicate that this channel is the epithelial sodium channel (ENaC). Whole-cell current-clamp showed that this ENaC had a small but significant contribution to the Vm. A mixed population of chloride channels was found in the chondrocyte using single channel and whole-cell current and voltage clamp recordings. This population consisted of a maxi-chloride channel and a calcium-activated chloride channel. A model of chondrocyte Vm was then developed combining the approach of Hodgkin and Huxley (1952b) with parameters measured in the patch clamp experiments. This model was able to simulate many of the effects of inhibition of channel conductances on the resting membrane potential. Whole-cell current clamp experiments using inhibitors of the ion conductances discovered previously, verified the models predictions. This thesis then tested the hypothesis that the depolarised Vm of chondrocytes facilitates volume regulation. Cell volume experiments discovered that at more negative Vm chondrocytes were unable to regulate their volume upon hypotonic challenge. At more positive potentia Is, cell volume recovery was significantly greater. This is likely to be due to the greater driving force for potassium efflux and suggests that the depolarised Vm is an adaptation which allows the chondrocyte to effectively regulate its volume.
36
Higgins, M. "Investigating ion channels of the nervous system". Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604038.
Testo completoAbstract (sommario):
In this thesis, I present data concerning several stages in synaptic transmission. I have investigated some of the channel proteins involved in the initiation and the propagation of changes of membrane potential in nerve cells. I have also studied the process of clathrin mediated endocytosis, which is essential in the propagation of messages across the synapses between cells. Firstly, the Shaker voltage-gated potassium channel has been expressed using the baculovirus-mediated expression system. The expressed protein binds to charybdotoxin. The expression of correctly folded protein was increased by calnexin co-expression, or by using a 'weaker' baculovirus promoter. The protein has been purified using a Ni2+-NTA column and consists of tetrameric particles when analysed by electron microscopy and image processing. The cyclic nucleotide-gated channel has been purified from bovine retina and studied by image processing and electron microscopy to yield a 35Å-resolution model. This shows a large domain, which I propose to be the membrane-spanning domain. Attached to this are two smaller domains. I suggest that these are the cyclic nucleotide-binding domains and that they hang below the channel in the cytosol where they act as an independently functioning pair of dimers. Preliminary expression and purification of the α-subunit of the olfactory CNG channel suggests that similar analyses of this protein will soon be possible. Finally, the role of AP180 and AP2 in the formation of clathrin coated vesicles has been investigated.
37
Warburton, Steven Peter Marc. "Calcium ion channels in insect skeletal muscle". Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363592.
Testo completo
38
Gu, Yuchun. "Investigation of ion channels on bone cells". Thesis, University of Birmingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369360.
Testo completo
39
Millar, Campbell. "3D simulation techniques for biological ion channels". Thesis, University of Glasgow, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401999.
Testo completo
40
Kirkovits, Gregory Joseph. "An approach to novel, artificial ion channels". Thesis, King's College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392151.
Testo completo
41
Steller, Laura Florentina. "Engineering of Light-Gated Artificial Ion Channels". Doctoral thesis, Technische Universität Dresden, 2006. https://tud.qucosa.de/id/qucosa%3A23931.
Testo completoAbstract (sommario):
The goal of this project is the development of artificial ion channels that can be actuated by light and thus controlled efficiently. Our artificial system is composed of two regions: the gate and the body part. The gate part is based on light-responsive azo groups while the body part is formed by calix[4]resorcinarene. Key of controlling mechanism is the conformational change between cis and trans isomers, which is translated into movement of the gate. Light-gated artificial ion channels are aimed at eliminating of the stochastic mechanism of artificial ion channels. Such a reversible photocontrol should be a powerful tool for using artificial ion channels as the basis for the development of new pharmaceuticals and drug delivery systems, as photoswitches, and in the field of microfluidics.
42
Adams, Leon. "Altered expression of ion channels in hyperinsulinism". Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/altered-expression-of-ion-channels-in-hyperinsulinism(81af0122-f772-44b5-86ed-b98aecd24880).html.
Testo completoAbstract (sommario):
The ability of the pancreatic β-cell to secrete insulin in response to changes in glucose concentration is the cornerstone of glucose homeostasis. The β-cell couples glucose metabolism to electrical activity via the modulation of ion channel activity. Defects in β-cell ion channels can result in the dysregulation of insulin secretion and, consequently, in glucose homeostasis. Congenital hyperinsulinism of infancy (CHI) is an inherited disorder of inappropriate insulin secretion often caused by gene defects in the subunits of KATP channels (ABCC8, KCNJ11). In 50% of CHI patients, no genetic basis has yet been discovered. I aimed to characterise the expression, and function, of two novel ion channel families in the healthy human pancreas and the hyperinsulinaemic pancreas.Hyperpolarisation-activated cyclic nucleotide-gated channels (HCN channels) are selective for K+ /Na+ under physiological conditions and are responsible for the rhythmic electrical behaviour (pacemaker behaviour) in the heart and brain. Two-pore potassium channels (K2P channels) are potassium-selective channels whose activity contributes to, and maintains, the resting membrane potential of living cells. HCN and K2P gene and protein expression was investigated by RT-PCR and immunofluorescence. HCN1, 2, 3, and 4 mRNA and mRNA from six K2P channels was detected in isolated mouse islets. Immunofluorescence revealed the presence of HCN1, HCN2 and HCN4 in mouse β-cells. The role of HCN channels in glucose-stimulated insulin secretion (GSIS) was assessed in isolated mouse islets. The HCN channel agonist lamotrigine had no effect on GSIS (n=3), but GSIS was significantly inhibited by the HCN channel blocker zatebradine (n=3) thereby confirming that HCN channels may play a role in glucose homeostasis. Tissue was isolated from adult control human pancreas and from six patients following pancreatectomy for CHI. HCN and K2P channel expression was also assessed in pancreatic tissue from ABCC8-knockout mice. HCN1-4 mRNA and the mRNA of four K2P channels were detected in islets isolated from adult control and CHI patient pancreatic tissue. Co-expression of HCN channel isoforms with insulin confirmed that HCN1, -2 and -4 were β-cell-specific in control human islets. By contrast, in all patient tissues expression of HCN channels was altered, and in 5 out of 6 cases, HCN channels were not expressed in β-cells. The K2P channel TWIK-1 was found to be expressed predominantly in the healthy human exocrine pancreas. In contrast, its expression was consistently detected in the β-cells of CHI patients. We found similar data for both HCN channels and TWIK-1 in islets of ABCC8-knockout mice, but not their litter-mate controls (n=3).These studies provide the first data on the expression of HCN and K2P channels in the human pancreas and reveal that CHI is associated with an altered expression profile of both ion channel families. Significantly, we found that HCN and K2P expression in β-cells is altered in CHI patients and we speculate that this is as a consequence of physiological remodelling.
43
Selepova, Pavla. "Single ion channel dynamics". Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=65415.
Testo completo
44
Liu, Pengyun, e 劉鵬云. "Design, synthesis, characterization and biological study of ion transporters". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206419.
Testo completo
45
Hasan, S. M. Raquibul. "Modulation of the TRPA1 and TRPV1 ion channels". Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708079.
Testo completo
46
Belfield, William James. "Flexibility and dynamics of ligand-gated ion channels". Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708057.
Testo completo
47
Berti, Claudio <1981>. "Numerical simulation of ion transport through ion channels and solid-state nanopores". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3370/1/berti_claudio_tesi.pdf.
Testo completoAbstract (sommario):
Ion channels are pore-forming proteins that regulate the flow of ions across biological cell membranes. Ion channels are
fundamental in generating and regulating the electrical activity of cells in the nervous system and the contraction of muscolar cells. Solid-state nanopores are nanometer-scale pores located in electrically insulating membranes. They can be adopted as detectors of specific molecules in electrolytic solutions. Permeation of ions from one electrolytic solution
to another, through a protein channel or a synthetic pore is a process of considerable importance and realistic analysis
of the main dependencies of ion current on the geometrical and compositional characteristics of these structures are highly
required.
The project described by this thesis is an effort to improve the understanding of ion channels by devising methods for computer simulation that can predict channel conductance from channel structure. This project describes theory, algorithms and implementation techniques used to develop a novel 3-D numerical simulator of ion channels and synthetic nanopores based on the Brownian Dynamics technique. This numerical simulator could represent a valid tool for the study of protein ion channel and synthetic nanopores, allowing to investigate at the atomic-level the complex electrostatic interactions that determine channel conductance and ion selectivity. Moreover it will provide insights on how parameters like temperature, applied voltage, and pore shape could influence ion translocation dynamics. Furthermore it will help making predictions of conductance of given channel structures and it will add information like electrostatic potential or ionic concentrations throughout the simulation domain helping the understanding of ion flow through membrane pores.
48
Berti, Claudio <1981>. "Numerical simulation of ion transport through ion channels and solid-state nanopores". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3370/.
Testo completoAbstract (sommario):
Ion channels are pore-forming proteins that regulate the flow of ions across biological cell membranes. Ion channels are
fundamental in generating and regulating the electrical activity of cells in the nervous system and the contraction of muscolar cells. Solid-state nanopores are nanometer-scale pores located in electrically insulating membranes. They can be adopted as detectors of specific molecules in electrolytic solutions. Permeation of ions from one electrolytic solution
to another, through a protein channel or a synthetic pore is a process of considerable importance and realistic analysis
of the main dependencies of ion current on the geometrical and compositional characteristics of these structures are highly
required.
The project described by this thesis is an effort to improve the understanding of ion channels by devising methods for computer simulation that can predict channel conductance from channel structure. This project describes theory, algorithms and implementation techniques used to develop a novel 3-D numerical simulator of ion channels and synthetic nanopores based on the Brownian Dynamics technique. This numerical simulator could represent a valid tool for the study of protein ion channel and synthetic nanopores, allowing to investigate at the atomic-level the complex electrostatic interactions that determine channel conductance and ion selectivity. Moreover it will provide insights on how parameters like temperature, applied voltage, and pore shape could influence ion translocation dynamics. Furthermore it will help making predictions of conductance of given channel structures and it will add information like electrostatic potential or ionic concentrations throughout the simulation domain helping the understanding of ion flow through membrane pores.
49
Victory, Jason G. G. "Ion channels and the myocardium : interactions between general anaesthetics and calcium channel blockers". Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253420.
Testo completo
50
Rea, Ruth. "Ion channel dysfunction in neurological disease : mutations of potassium channels and glycine receptors". Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271822.
Testo completo