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1

Kim, Robin Yongkyu. "Mechanistic insights into retigabine modulation of neuronal KCNQ channels." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/62625.

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The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.<br>Medicine, Faculty of<br>Anesthesiology, Pharmacology and Therapeutics, Department of<br>Graduate
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2

Mruk, Karen. "Small Molecule Investigation of KCNQ Potassium Channels: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/621.

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Voltage-gated K+ channels associate with multiple regulatory proteins to form complexes with diverse gating properties and pharmacological sensitivities. Small molecules which activate or inhibit channel function are valuable tools for dissecting the assembly and function of these macromolecular complexes. My thesis focuses on the discovery and use of small molecules to probe the structure and function of the KCNQ family of voltage-gated K+ channels. One protein that obligatorily assembles with KCNQ channels to mediate proper assembly, trafficking, and gating is the calcium sensor, calmodulin.
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3

Gage, Steven D. "Structural and Functional Studies of the KCNQ1-KCNE K+ Channel Complex: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/409.

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KCNQ1 is a homotetrameric voltage-gated potassium channel expressed in cardiomyocytes and epithelial tissues. However, currents arising from KCNQ1 have never been physiologically observed. KCNQ1 is able to provide the diverse potassium conductances required by these distinct cell types through coassembly with and modulation by type I transmembrane β-subunits of the KCNE gene family. KCNQ1-KCNE K+ channels play important physiological roles. In cardiac tissues the association of KCNQ1 with KCNE1 gives rise to IKs, the slow delayed outwardly rectifying potassium current. IKs is in part responsib
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4

Cerina, Manuela [Verfasser], and Thomas [Akademischer Betreuer] Budde. "The role of KCNQ channels in the thalamus / Manuela Cerina ; Betreuer: Thomas Budde." Münster : Universitäts- und Landesbibliothek Münster, 2013. http://d-nb.info/1141577968/34.

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5

Brennan, Sean. "KV7 potassium channels : a focus on human intra-pulmonary arteries." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/kv7-potassium-channels-a-focus-on-human-intrapulmonary-arteries(46f5ff0e-1674-4ab1-916d-2f43e3c585e5).html.

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Pulmonary arterial hypertension (PAH) is a disease in which pulmonary vascular resistance increases. The cell membrane of pulmonary artery smooth muscle cells (PASMC) in PAH patients is depolarised, resulting in disrupted Ca2+ signalling leading to smooth muscle constriction and PASMC proliferation and migration. In rat pulmonary artery (PA) smooth muscle the KV7 K+ channels, encoded by the KCNQ genes, have been proposed to contribute to the resting K+ current, promoting low resting tone by maintaining a negative membrane potential and low intracellular Ca2+. KV7 channel activating drugs have
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6

Delank, Anna-Katharina [Verfasser], and Sven [Akademischer Betreuer] Meuth. "The role of KCNQ-channels in the pathophysiology of multiple sclerosis / Anna-Katharina Delank ; Betreuer: Sven Meuth." Münster : Universitäts- und Landesbibliothek Münster, 2021. http://d-nb.info/1229512187/34.

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7

Piccinin, Sonia. "The role of group I mGluRs and KCNQ/M channels in synaptic and non-synaptic neuronal activity in hippocampal slices." Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486110.

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The overall aim of this work was to establish the role of group I mGluR and KCNQ/M channels in aspects of the neurophysiology of area CA1 of the rat hippocampus. Specifically we studied the role of these putative drug targets in a form of epileptiform activity and in the slow fEPSP recorded using extracellular methods. First, we have described here the extracellular recording of an excitatory slow fEPSP which is predominantly mediated by acetylcholine, as evidenced by the increase in physostigmine and inhibition in the presence of atropine. This type of response is significantly enhanced by tw
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8

Prole, David L. "Intrinsic functional properties of neuronal KCNQ2/KCNQ3 potassium channels : insights into channel structure." Thesis, University of Bristol, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.400272.

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9

Morin, Trevor J. "Chemical-Biological Investigation of KCNQ1/KCNE K+ Channel Complexes: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/398.

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KCNE β-subunits modulate KCNQ1 (Q1) voltage-gate K+channels providing the current diversity required for Q1 channels to function in a wide variety of cell types and tissues. In the present thesis, the stoichiometry of KCNE1 (E1) β-subunits in functioning Q1 channels is investigated, along with the formation of heteromeric channel complexes, complexes containing 2 different KCNE β-subunits. The chemical approaches used to answer these questions were then expanded to generate a novel labeling reagent. To determine the stoichiometry of the Q1/E1 complex, I devised an iterative subunit counting ap
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10

Shimizu, Atsuya, Ryoko Niwa, Zhibo Lu, Haruo Honjo, and Kaichiro Kamiya. "Effects of Dronedarone on HERG and KCNQ1/KCNE1 Channels." Research Institute of Environmental Medicine, Nagoya University, 2003. http://hdl.handle.net/2237/7585.

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11

Choi, Eun Kyung. "Regulation of KCNQ1 potassium channel trafficking and gating by KCNE1 and KCNE3 /." Access full-text from WCMC, 2009. http://proquest.umi.com/pqdweb?did=1692648191&sid=1&Fmt=2&clientId=8424&RQT=309&VName=PQD.

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12

Cavaliere, Sonia. "Electrophysiological, pharmacological and behavioural characterisation of the Drosophila KCNQ channel." Thesis, University of Bristol, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555722.

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There are five KCNQ (Kv7) channels in humans. The cardiac KCNQl channel when assembled with KCNEl mediates the cardiac IKs current with mutations causing short and long QT cardiac arrhythmias. Neuronal KCNQ2/3 channels form the M-current that controls excitability of most neurons with mutations causing a form of epilepsy called benign neonatal familial convulsions. KCNQ4 mutations cause deafuess and age dependent hearing loss. KCNQ5 is expressed in the hippocampus and cortex and is also thought to regulate excitability and plasticity in these brain regions. Drosophila has a single KCNQ channel
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13

Rapetti-Mauss, Raphaël. "Estrogen Regulation of the Potassium Channel KCNQ1 : KCNE3 in colonic epithelium." Thesis, Montpellier 1, 2013. http://www.theses.fr/2013MON1T005/document.

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Contexte: KCNQ1: KCNE3 joue un rôle essentiel dans le mécanisme de sécrétion du Cl- dans le côlon distal. Ce canal K+ génère la force électromotrice nécessaire à la sécrétion apicale de Cl- par le recyclage basolatéral de K+. Il a précédemment été démontré que l'hormone stéroïde œstrogène (17β-œstradiol, E2) induit, spécifiquement chez la femelle un effet anti-sécrétoire dans les cryptes de côlon de rat via l'inhibition de KCNQ1:KCNE3. Cette thèse a pour but de déterminer les mécanismes moléculaires mise en jeu dans la régulation des fonctions du canal KCNQ1 par l'œstrogène, en particulier dan
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14

Rocheleau, Jessica Marie. "Effect of KCNE1 and KCNE3 Accessory Subunits on KCNQ1 Potassium Channel Function: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/397.

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The KCNE1 and KCNE3 type I transmembrane-spanning β-subunits assemble with the KCNQ1 voltage-gated K+ channel to afford membrane-embedded complexes with dramatically different properties. Assembly with KCNE1 produces the very slowly activating and deactivating IKs current that shapes the repolarization phase of cardiac action potentials. Genetic mutations in KCNQ1 or KCNE1 that reduce IKs current cause long QT syndrome and predispose affected individuals to potentially fatal cardiac arrhythmias. In contrast, complexes formed between KCNQ1 and KCNE3 produce rapidly activating and mostly voltage
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15

Wang, Wei-Ting. "Defining the molecular mechanisms of subtype-specific KCNQ2/3 potassium channel activators." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/57894.

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Retigabine is the first approved anti-epileptic drug that acts via activation of voltage-gated potassium channels, targeting KCNQ channels that underlie the neuronal M-current. Retigabine exhibits little specificity between KCNQ2-5, which all contain a Trp residue in the pore domain that is essential for retigabine actions. The retigabine analog ICA 069673 (‘ICA73’) exhibits much stronger effects than retigabine on KCNQ2 channels, including a large hyperpolarizing shift of the voltage-dependence of activation, and roughly two-fold enhancement of peak current. Unlike retigabine, ICA73 exhibits
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16

Royal, Alice. "The regulation of trafficking and function of KCNQ1 potassium channels by phosphatidylinositol-4,5-bisphosphate." Thesis, Queen Mary, University of London, 2017. http://qmro.qmul.ac.uk/xmlui/handle/123456789/25940.

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The IKs current constitutes part of the repolarisation reserve in the human myocardium, and whilst it does not play a major role at resting heart rates, it becomes a crucial component of repolarisation in the setting of increased sympathetic tone and high heart rates. The formation of the IKs current requires the KCNQ1 α-subunit and the KCNE1 β-subunit. Mutations in either of these subunits can lead to long QT syndrome types 1 and 5, respectively. Loss-of-function mutations in the IKs channel can reduce the repolarisation reserve and lead to action potential prolongation, predisposing to letha
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17

Gao, Xiaojie. "Regulation and functions of burst firing: the role of KCNQ3 potassium channels in vivo." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/22144.

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Ionenkanäle leiten Ionenströme über neuronale Membranen, wodurch Aktionspotentiale erzeugt und weitergeleitet werden. Sie spielen eine zentrale Rolle bei der Regulierung der Erregbarkeit und des Aktivierungsverhaltens von Neuronen. KCNQs sind eine wichtige Familie von spannungsgesteuerten Kaliumkanälen; ihre Dysfunktion kann zu verschiedenen neurologischen Krankheiten führen, einschließlich Erkrankung an Epilepsie und Taubheit. Es wurde gezeigt, dass KCNQ2 und KCNQ3 den M-Strom verantwortlich sind. Letzterer ist für die Regulierung des repetitiven Feuerns von Pyramidenzellen entscheidend
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18

Gao, Xiaojie [Verfasser]. "Regulation and functions of burst firing: the role of KCNQ3 potassium channels in vivo / Xiaojie Gao." Berlin : Humboldt-Universität zu Berlin, 2020. http://d-nb.info/1222973294/34.

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19

Bartos, Daniel C. "Mechanistic Basis for Atrial and Ventricular Arrhythmias Caused by KCNQ1 Mutations." UKnowledge, 2013. http://uknowledge.uky.edu/physiology_etds/8.

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Cardiac arrhythmias are caused by a disruption of the normal initiation or propagation of electrical impulses in the heart. Hundreds of mutations in genes encoding ion channels or ion channel regulatory proteins are linked to congenital arrhythmia syndromes that increase the risk for sudden cardiac death. This dissertation focuses on how mutations in a gene (KCNQ1) that encodes a voltage-gated K+ ion channel (Kv7.1) can disrupt proper channel function and lead to abnormal repolarization of atrial and ventricular cardiomyocytes. In the heart, Kv7.1 coassembles with a regulatory protein to condu
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20

Chandrasekhar, Kshama D. "Glycosylation, Assembly and Trafficking of Cardiac Potassium Channel Complexes: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/483.

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KCNE peptides are a class of type I transmembrane ß-subunits that assemble with and modulate the gating and ion conducting properties of a variety of voltage-gated K+ channels. Accordingly, mutations that affect the assembly and trafficking of K+ channel/KCNE complexes give rise to disease. The cellular mechanisms that oversee KCNE peptide assembly with voltage-gated K+ channels have yet to be elucidated. In Chapter II, we show that KCNE1 peptides are retained in the early stages of the secretory pathway until they co-assemble with KCNQ1 K+ channel subunits. Co-assembly with KCNQ1 channel subu
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21

Berenguier, Camille. "Exploration de la fonction du canal potassique KCNQ1 dans l'homéostasie de la crypte colique." Electronic Thesis or Diss., Université Côte d'Azur, 2023. http://www.theses.fr/2023COAZ6025.

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Le rôle des canaux ioniques dans les processus cancéreux a émergé ces dernières années et constitue un domaine en plein essor. Il a notamment été montré, d'une part que l'expression de certains canaux ioniques était dérégulée dans les cancers et d'autre part que les canaux ioniques pouvaient réguler diverses voies de signalisation cellulaire. L'équilibre des voies de signalisation est essentiel en physiologie. Dans l'épithélium du colon, cet équilibre est d'autant plus crucial que les cellules sont soumises à un renouvèlement rapide, régit par l'action conjointe de plusieurs voies de signalisa
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22

Kubota, Tomoyuki. "Evidence for a Single Nucleotide Polymorphism in the KCNQ1 Potassium Channel that Underlies Susceptibility to Life-Threatening Arrhythmias." Kyoto University, 2002. http://hdl.handle.net/2433/149687.

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23

Dixit, Gunjan. "Investigating the Structural Dynamics and Topology of Human KCNQ1 Potassium Ion Channel using Solid-State NMR and EPR Spectroscopy." Miami University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=miami1563317786011624.

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24

Albrecht, Julie [Verfasser]. "The effect of the KV7/KCNE 1 inhibitor JNJ 303 on heart slices and the L-type calcium channel of cardiac cells / Julie Albrecht." Köln : Deutsche Zentralbibliothek für Medizin, 2017. http://d-nb.info/1130707415/34.

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25

Solé, i. Codina Laura. "Role of KCN E4 on the voltage gated potassium channel Kv1.3 = Paper de KCNE4 en el canal de potassi dependent de voltage Kv1.3." Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/129685.

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Voltage gated potassium channels (Kv) play important roles in different biological process such as generation and propagation of the nerve pulse and the cardiac action potential, promotion of insulin secretion, cell volume control, induction of cell proliferation, apoptosis, migration and initiation of many signaling pathways. Kv channels can homo- or hetero- tetramerize. The composition of the channel modulates their surface expression and serves as a mechanism for regulating channel activity. Kv channel interaction with accessory subunits provides mechanisms for channels to respond to stimul
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26

Athanasiadu, Despina [Verfasser]. "Investigations on subunit specific assembly and structure function studies of the voltage sensor in KCNQ potassium channels / von Despina Athanasiadu." 2008. http://d-nb.info/987268341/34.

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27

Bilet, Arne [Verfasser]. "Influence of the extracellular potassium concentration on the biophysical properties of KCNQ2, KCNQ3, and KCNQ5 voltage-gated potassium channels / vorgelegt von Arne Bilet." 2010. http://d-nb.info/1006372148/34.

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28

Peng, Gary. "Gating mechanisms underlying deactivation slowing by atrial fibrillation mutations and small molecule activators of KCNQ1." Thesis, 2017. https://doi.org/10.7916/D8R49WF7.

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Ion channels are membrane proteins that facilitate electrical signaling in important physiological processes, such as the rhythmic contraction of the heart. KCNQ1 is the pore-forming subunit of a voltage-gated potassium channel that assembles with the β-subunit KCNE1 in the heart to generate the IKs current, which is critical to cardiac action potential repolarization and electrical conduction in the heart. Mutations in IKs subunits can cause potentially lethal arrhythmia, including long QT syndrome, short QT syndrome, and atrial fibrillation. Each channel consists of four voltage-sensing d
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29

Ma, Lijuan [Verfasser]. "Mutational analysis of KCNQ1 (Kv 7.1) channel gating / by Lijuan Ma." 2007. http://d-nb.info/986483362/34.

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30

Jing-Jer and 陳敬哲. "Functional study of phosphotase inhibitors and PMA on KCNQ4 potassium channel." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/24223983664737223589.

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碩士<br>中山醫學大學<br>生物醫學科學學系碩士班<br>98<br>We would like to understand the relationship between KCNQ4 potassium channel and phosphorylation. HEK293t cell and Xenopous laevis oocyte ion channel expression systems would be our choice. To use two electrodes voltage clamp (TEVC) and whole cell voltage clamp recording KCNQ4 potassium current which expressed on Xenopous laevis oocyte and HEK293t cell, and treating with phosphorylation chemicals to increase or decrease phospohryaltion state. On the other hand, we predict the possible phosphorylation site of KCNQ4 potassium channel by Bioimformatics phospho
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31

Wehling, Erica R. "Regulation of KCNQ1 potassium channels by vasoactive intestinal peptide in liver and colonic epithelial cells." 2007. http://proquest.umi.com/pqdweb?did=1320950671&sid=19&Fmt=2&clientId=39334&RQT=309&VName=PQD.

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Thesis (M.A.)--State University of New York at Buffalo, 2007.<br>Title from PDF title page (viewed on Nov. 28, 2007) Available through UMI ProQuest Digital Dissertations. Thesis adviser: Duffey, Michael E. Includes bibliographical references.
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32

"Regulation of Ion Channel Physiology in Airway Epithelial cells in response to Influenza A Virus Infection." Thesis, 2013. http://hdl.handle.net/10388/ETD-2013-08-1133.

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Epithelial cells lining the upper airways are characterized by low sodium absorption and elevated chloride secretion. Together, the movement of these ions creates the osmotic drive to hydrate the airways. Recent studies indicate that influenza is capable of directly modulating the vectorial transport of sodium and chloride ions. However, the direct impact of influenza has not been studied with respect to potassium channels. This is significant because potassium conductance creates the driving force for chloride secretion. Disruptions to this process leads to edema formation in the lungs and ca
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33

Chan, Priscilla Jay. "Functional and Biochemical Characterization of KCNQ1/KCNE1 Subunit Interactions in the Cardiac IKs Potassium Channel." Thesis, 2011. https://doi.org/10.7916/D84X5FRQ.

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The IKs potassium channel, critical to control of heart electrical activity, requires assembly of pore-forming alpha subunits (KCNQ1) and accessory beta (KCNE1) subunits. IKs is the slowly activating component of delayed rectifier K+ current in the heart and is a major contributor to the timing of repolarization of the cardiomyocyte membrane potential. Inherited mutations in either IKs channel subunit are associated with cardiac arrhythmia syndromes, including long QT syndrome (LQTS), short QT syndrome (SQTS) and familial atrial fibrillation (FAF). The biophysical properties of IKs channel cur
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34

Benjamin, Pablo Juan Lorenzo. "The Diversity of FHF-mediated Ion Channel Regulation." Diss., 2015. http://hdl.handle.net/10161/11360.

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<p>Fibroblast growth factor homologous factors (FHFs) are noncanonical members of the fibroblast growth factor family (FGFs, FGF11-FGF14) that bind directly to voltage gated sodium channels (VGSCs), thereby regulating channel activity and consequently neuronal excitability. Mutations in FGF14 cause spinocerebellar ataxia while FGF13 is a candidate for X-linked mental retardation. Since FGF13 and FGF14 are nearly identical within their respective VGSC-interacting domains, those distinct pathological consequences have generally been attributed to regional differences in expression. I have shown
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35

Gwan-Hong and 陳冠宏. "Functional study of the phosphorylation effect on human KCNQ4 potassium channel via heterologous expression in Xenopus laevis oocytes." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/54098914165832471793.

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碩士<br>中山醫學大學<br>生物醫學科學學系碩士班<br>95<br>The purpose of this study was to investigate the effect of phosphorylation on KCNQ4 potassium ion channel. The human KCNQ4 cRNA was purified from HpaⅠlinearized plasmid DNA, then inject it into the Xenopus laevis oocytes by microinjection to heterologous express the KCNQ4 potassium ion channel on cell membrane. Two-Electrode Voltage-Clamp (TEVC) technique was used for the measurement of function of KCNQ4. The treatment of protein phosphorylation modulators was utilized to observe the changes of electrical parameters of KCNQ4 channel including the ion curren
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