請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65204
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 潘建源(Chien-Yuan Pan) | |
dc.contributor.author | Shao-Han Chang | en |
dc.contributor.author | 張邵涵 | zh_TW |
dc.date.accessioned | 2021-06-16T23:29:47Z | - |
dc.date.available | 2014-08-01 | |
dc.date.copyright | 2012-08-01 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-30 | |
dc.identifier.citation | Bahler, M., and Rhoads, A. (2002). Calmodulin signaling via the IQ motif. FEBS Lett 513, 107-113.
Beckh, S., Noda, M., Lubbert, H., and Numa, S. (1989). Differential regulation of three sodium channel messenger RNAs in the rat central nervous system during development. EMBO J 8, 3611-3616. Bezzina, C., Veldkamp, M.W., van Den Berg, M.P., Postma, A.V., Rook, M.B., Viersma, J.W., van Langen, I.M., Tan-Sindhunata, G., Bink-Boelkens, M.T., van Der Hout, A.H., et al. (1999). A single Na+ channel mutation causing both long-QT and Brugada syndromes. Circ Res 85, 1206-1213. Black, D.J., Halling, D.B., Mandich, D.V., Pedersen, S.E., Altschuld, R.A., and Hamilton, S.L. (2005). Calmodulin interactions with IQ peptides from voltage-dependent calcium channels. Am J Physiol Cell Physiol 288, C669-676. Black, J.A., Liu, S., Tanaka, M., Cummins, T.R., and Waxman, S.G. (2004). Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Pain 108, 237-247. Bredt, D.S., and Snyder, S.H. (1989). Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci U S A 86, 9030-9033. Carafoli, E., Santella, L., Branca, D., and Brini, M. (2001). Generation, control, and processing of cellular calcium signals. Crit Rev Biochem Mol Biol 36, 107-260. Catterall, W.A., Kalume, F., and Oakley, J.C. (2010). Nav1.1 channels and epilepsy. J Physiol 588, 1849-1859. Chagot, B., and Chazin, W.J. (2011). Solution NMR structure of Apo-calmodulin in complex with the IQ motif of human cardiac sodium channel Nav1.5. J Mol Biol 406, 106-119. Chagot, B., Potet, F., Balser, J.R., and Chazin, W.J. (2009). Solution NMR structure of the C-terminal EF-hand domain of human cardiac sodium channel Nav1.5. J Biol Chem 284, 6436-6445. Choi, J.S., Hudmon, A., Waxman, S.G., and Dib-Hajj, S.D. (2006). Calmodulin regulates current density and frequency-dependent inhibition of sodium channel Nav1.8 in DRG neurons. J Neurophysiol 96, 97-108. Cooper, G.A., Seymour, A., Cassidy, M.T., and Oliver, J.S. (1999). A study of methadone in fatalities in the Strathclyde Region, 1991-1996. Med Sci Law 39, 233-242. DeMaria, C.D., Soong, T.W., Alseikhan, B.A., Alvania, R.S., and Yue, D.T. (2001). Calmodulin bifurcates the local Ca2+ signal that modulates P/Q-type Ca2+ channels. Nature 411, 484-489. Deschenes, I., Neyroud, N., DiSilvestre, D., Marban, E., Yue, D.T., and Tomaselli, G.F. (2002). Isoform-specific modulation of voltage-gated Na+ channels by calmodulin. Circ Res 90, E49-57. Ellis, S.B., Williams, M.E., Ways, N.R., Brenner, R., Sharp, A.H., Leung, A.T., Campbell, K.P., McKenna, E., Koch, W.J., Hui, A., et al. (1988). Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel. Science 241, 1661-1664. Endoh, M., Yanagisawa, T., Taira, N., and Blinks, J.R. (1986). Effects of new inotropic agents on cyclic nucleotide metabolism and calcium transients in canine ventricular muscle. Circulation 73, III117-133. Feldkamp, M.D., Yu, L., and Shea, M.A. (2011). Structural and energetic determinants of apo calmodulin binding to the IQ motif of the Nav1.2 voltage-dependent sodium channel. Structure 19, 733-747. Fisone, G., Cheng, S.X., Nairn, A.C., Czernik, A.J., Hemmings, H.C., Jr., Hoog, J.O., Bertorello, A.M., Kaiser, R., Bergman, T., Jornvall, H., et al. (1994). Identification of the phosphorylation site for cAMP-dependent protein kinase on Na+,K+-ATPase and effects of site-directed mutagenesis. J Biol Chem 269, 9368-9373. Gordon, D., Merrick, D., Auld, V., Dunn, R., Goldin, A.L., Davidson, N., and Catterall, W.A. (1987). Tissue-specific expression of the RI and RII sodium channel subtypes. Proc Natl Acad Sci U S A 84, 8682-8686. Gu, C., and Cooper, D.M. (1999). Calmodulin-binding sites on adenylyl cyclase type VIII. J Biol Chem 274, 8012-8021. Guy, H.R., and Seetharamulu, P. (1986). Molecular model of the action potential sodium channel. Proc Natl Acad Sci U S A 83, 508-512. Heinemann, S.H., Terlau, H., Stuhmer, W., Imoto, K., and Numa, S. (1992). Calcium channel characteristics conferred on the sodium channel by single mutations. Nature 356, 441-443. Herzog, R.I., Liu, C., Waxman, S.G., and Cummins, T.R. (2003). Calmodulin binds to the C terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties. J Neurosci 23, 8261-8270. Hillsley, K., Lin, J.H., Stanisz, A., Grundy, D., Aerssens, J., Peeters, P.J., Moechars, D., Coulie, B., and Stead, R.H. (2006). Dissecting the role of sodium currents in visceral sensory neurons in a model of chronic hyperexcitability using Nav1.8 and Nav1.9 null mice. J Physiol 576, 257-267. Hirschberg, B., Rovner, A., Lieberman, M., and Patlak, J. (1995). Transfer of twelve charges is needed to open skeletal muscle Na+ channels. J Gen Physiol 106, 1053-1068. Hodgkin, A.L., and Huxley, A.F. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117, 500-544. Isom, L.L., De Jongh, K.S., Patton, D.E., Reber, B.F., Offord, J., Charbonneau, H., Walsh, K., Goldin, A.L., and Catterall, W.A. (1992). Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. Science 256, 839-842. Jurkat-Rott, K., Holzherr, B., Fauler, M., and Lehmann-Horn, F. (2010). Sodium channelopathies of skeletal muscle result from gain or loss of function. Pflugers Arch 460, 239-248. Jurkat-Rott, K., Weber, M.A., Fauler, M., Guo, X.H., Holzherr, B.D., Paczulla, A., Nordsborg, N., Joechle, W., and Lehmann-Horn, F. (2009). K+-dependent paradoxical membrane depolarization and Na+ overload, major and reversible contributors to weakness by ion channel leaks. Proc Natl Acad Sci U S A 106, 4036-4041. Kaplan, M.R., Cho, M.H., Ullian, E.M., Isom, L.L., Levinson, S.R., and Barres, B.A. (2001). Differential control of clustering of the sodium channels Nav1.2 and Nav1.6 at developing CNS nodes of Ranvier. Neuron 30, 105-119. Kohama, K., Saida, K., Hirata, M., Kitaura, T., and Ebashi, S. (1986). Superprecipitation is a model for in vitro contraction superior to ATPase activity. Jpn J Pharmacol 42, 253-260. Konishi, M. (1998). Cytoplasmic free concentrations of Ca2+ and Mg2+ in skeletal muscle fibers at rest and during contraction. Jpn J Physiol 48, 421-438. Lee, A., Wong, S.T., Gallagher, D., Li, B., Storm, D.R., Scheuer, T., and Catterall, W.A. (1999). Ca2+/calmodulin binds to and modulates P/Q-type calcium channels. Nature 399, 155-159. Lehmann-Horn, F., and Jurkat-Rott, K. (1999). Voltage-gated ion channels and hereditary disease. Physiol Rev 79, 1317-1372. Maingret, F., Coste, B., Padilla, F., Clerc, N., Crest, M., Korogod, S.M., and Delmas, P. (2008). Inflammatory mediators increase Nav1.9 current and excitability in nociceptors through a coincident detection mechanism. J Gen Physiol 131, 211-225. Meisler, M.H., and Kearney, J.A. (2005). Sodium channel mutations in epilepsy and other neurological disorders. J Clin Invest 115, 2010-2017. Messner, D.J., and Catterall, W.A. (1985). The sodium channel from rat brain. Separation and characterization of subunits. J Biol Chem 260, 10597-10604. Mori, M., Konno, T., Ozawa, T., Murata, M., Imoto, K., and Nagayama, K. (2000). Novel interaction of the voltage-dependent sodium channel (VDSC) with calmodulin: does VDSC acquire calmodulin-mediated Ca2+-sensitivity? Biochemistry 39, 1316-1323. Mori, Y., Mikala, G., Varadi, G., Kobayashi, T., Koch, S., Wakamori, M., and Schwartz, A. (1996). Molecular pharmacology of voltage-dependent calcium channels. Jpn J Pharmacol 72, 83-109. Nairn, A.C., and Picciotto, M.R. (1994). Calcium/calmodulin-dependent protein kinases. Semin Cancer Biol 5, 295-303. Noda, M., Shimizu, S., Tanabe, T., Takai, T., Kayano, T., Ikeda, T., Takahashi, H., Nakayama, H., Kanaoka, Y., Minamino, N., et al. (1984). Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature 312, 121-127. Patrick Harty, T., and Waxman, S.G. (2007). Inactivation properties of sodium channel Nav1.8 maintain action potential amplitude in small DRG neurons in the context of depolarization. Mol Pain 3, 12. Peracchia, C., Wang, X.G., and Peracchia, L.L. (2000). Slow gating of gap junction channels and calmodulin. J Membr Biol 178, 55-70. Peterson, B.Z., Lee, J.S., Mulle, J.G., Wang, Y., de Leon, M., and Yue, D.T. (2000). Critical determinants of Ca2+-dependent inactivation within an EF-hand motif of L-type Ca(2+) channels. Biophys J 78, 1906-1920. Pitt, G.S. (2007). Calmodulin and CaMKII as molecular switches for cardiac ion channels. Cardiovasc Res 73, 641-647. Ragsdale, D.S. (2008). How do mutant Nav1.1 sodium channels cause epilepsy? Brain Res Rev 58, 149-159. Rhoads, A.R., and Friedberg, F. (1997). Sequence motifs for calmodulin recognition. FASEB J 11, 331-340. Rivolta, I., Abriel, H., Tateyama, M., Liu, H., Memmi, M., Vardas, P., Napolitano, C., Priori, S.G., and Kass, R.S. (2001). Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes. J Biol Chem 276, 30623-30630. Rusconi, R., Combi, R., Cestele, S., Grioni, D., Franceschetti, S., Dalpra, L., and Mantegazza, M. (2009). A rescuable folding defective Nav1.1 (SCN1A) sodium channel mutant causes GEFS+: common mechanism in Nav1.1 related epilepsies? Hum Mutat 30, E747-760. Sarhan, M.F., Tung, C.C., Van Petegem, F., and Ahern, C.A. (2012). Crystallographic basis for calcium regulation of sodium channels. Proc Natl Acad Sci U S A 109, 3558-3563. Schlief, T., Schonherr, R., Imoto, K., and Heinemann, S.H. (1996). Pore properties of rat brain II sodium channels mutated in the selectivity filter domain. Eur Biophys J 25, 75-91. Shah, V.N., Wingo, T.L., Weiss, K.L., Williams, C.K., Balser, J.R., and Chazin, W.J. (2006). Calcium-dependent regulation of the voltage-gated sodium channel hH1: intrinsic and extrinsic sensors use a common molecular switch. Proc Natl Acad Sci U S A 103, 3592-3597. Simkin, D., and Bendahhou, S. (2011). Skeletal muscle Na+ channel disorders. Front Pharmacol 2, 63. Sinha, S.K., Gao, N., Guo, Y., and Yuan, D. (2010). Mechanism of induction of NK activation by 2B4 (CD244) via its cognate ligand. J Immunol 185, 5205-5210. Struyk, A.F., Scoggan, K.A., Bulman, D.E., and Cannon, S.C. (2000). The human skeletal muscle Na channel mutation R669H associated with hypokalemic periodic paralysis enhances slow inactivation. J Neurosci 20, 8610-8617. Stuhmer, W., Conti, F., Suzuki, H., Wang, X.D., Noda, M., Yahagi, N., Kubo, H., and Numa, S. (1989). Structural parts involved in activation and inactivation of the sodium channel. Nature 339, 597-603. Sun, Y.M., Favre, I., Schild, L., and Moczydlowski, E. (1997). On the structural basis for size-selective permeation of organic cations through the voltage-gated sodium channel. Effect of alanine mutations at the DEKA locus on selectivity, inhibition by Ca2+ and H+, and molecular sieving. J Gen Physiol 110, 693-715. Tan, H.L., Kupershmidt, S., Zhang, R., Stepanovic, S., Roden, D.M., Wilde, A.A., Anderson, M.E., and Balser, J.R. (2002). A calcium sensor in the sodium channel modulates cardiac excitability. Nature 415, 442-447. Theoharis, N.T., Sorensen, B.R., Theisen-Toupal, J., and Shea, M.A. (2008). The neuronal voltage-dependent sodium channel type II IQ motif lowers the calcium affinity of the C-domain of calmodulin. Biochemistry 47, 112-123. Veldkamp, M.W., Viswanathan, P.C., Bezzina, C., Baartscheer, A., Wilde, A.A., and Balser, J.R. (2000). Two distinct congenital arrhythmias evoked by a multidysfunctional Na+ channel. Circ Res 86, E91-97. Williams, J.H., and Klug, G.A. (1995). Calcium exchange hypothesis of skeletal muscle fatigue: a brief review. Muscle Nerve 18, 421-434. Wingo, T.L., Shah, V.N., Anderson, M.E., Lybrand, T.P., Chazin, W.J., and Balser, J.R. (2004). An EF-hand in the sodium channel couples intracellular calcium to cardiac excitability. Nat Struct Mol Biol 11, 219-225. Young, K.A., and Caldwell, J.H. (2005). Modulation of skeletal and cardiac voltage-gated sodium channels by calmodulin. J Physiol 565, 349-370. Yu, F.H., and Catterall, W.A. (2003). Overview of the voltage-gated sodium channel family. Genome Biol 4, 207. Yu, F.H., Mantegazza, M., Westenbroek, R.E., Robbins, C.A., Kalume, F., Burton, K.A., Spain, W.J., McKnight, G.S., Scheuer, T., and Catterall, W.A. (2006). Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci 9, 1142-1149. Ziane, R., Huang, H., Moghadaszadeh, B., Beggs, A.H., Levesque, G., and Chahine, M. (2010). Cell membrane expression of cardiac sodium channel Nav1.5 is modulated by alpha-actinin-2 interaction. Biochemistry 49, 166-178. Zuhlke, R.D., Pitt, G.S., Deisseroth, K., Tsien, R.W., and Reuter, H. (1999). Calmodulin supports both inactivation and facilitation of L-type calcium channels. Nature 399, 159-162. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65204 | - |
dc.description.abstract | 電壓依賴型鈉離子通道(voltage-gated sodium channel, VGSCs)在引起細胞動作電位(action potential)及動作電位的傳遞上扮演重要角色。鈣調素(calmodulin)是一胞內鈣離子感受蛋白,可透過膜通道蛋白C端上高度保守性之蛋白序列IQ motif對許多不同類型之膜通道蛋白進行調控。前人的研究當中指出,鈣調素對於不同的類型鈉離子通道蛋白之IQ motif具有不同親和能力。本實驗當中,將鈣調素(CaM)以及失去正常鈣離子結合功能之突變型鈣調素(CaM1234)與電壓依賴型鈉離子通道(Nav1.4)同時表現於人類胚胎腎臟細胞(human embryonic kidney cells, HEK 293T),鈣調素(CaM)和突變型鈣調素(CaM1234)可增加流入細胞之鈉離子的電流量,且並不改變鈉離子通道Nav1.4其活化(activation)與不活化(inactivation)特性。提高pipette solution中鈣離子濃度至10μM,鈣調素和突變型鈣調素均會增加鈉離子電流,而鈣調素會縮短鈉離子通道由不活化(inactivation)狀態再回到通道可再開啟的時間。若降低pipette solution中鈣離子濃度至0.2μM,其通道蛋白由不活化狀態恢復至通道可再開啓的時間則不受影響。此外,鈣調素在Nav1.1上亦有類似的調控情形,會增加鈉離子的電流。 經由西方點墨法(western blot)已及細胞免疫染色的分析,發現細胞膜上鈉離子通道的表現量有增加的現象。另外,在IQ motif上進行點突變亦會觀察到上述兩項改變。實驗結果顯示鈣調素可藉由感應胞內鈣離子濃度的變化進一步調控電壓依賴型鈉離子通道之特性。 | zh_TW |
dc.description.abstract | Voltage-gated sodium channels (VGSCs) are essential for the initiation and propagation of action potentials in excitable cells. Calmodulin (CaM), a calcium sensor protein, regulates many types of ionic channels by binding to the highly conserved IQ motif at the intracellular C-terminal. Several reports have suggested that CaM has differential binding affinities with peptides containing the IQ motifs of various Na+ channels. However, it is not clear how CaM modulate the Na+ channel activities. In this report, we co-expressed CaM and Nav1.4 in 293T cells and measured the Na+ currents by patch-clamp technique in whole-cell mode. Both CaM and the Ca2+-binding deficient mutant, CaM1234, enhanced the current amplitude without changing the activation and inactivation properties. Elevating the Ca2+ concentration in the pipette solution to 10 μM, CaM and CaM1234 further increased the Na+ current; however, only CaM shortened the recovery time. While with 0.2 μM Ca2+ in the pipette solution, both CaM and CaM1234 enhanced the Na+ currents but had no effect on recovery time. Staining the expression level of Nav1.4 with a specific antibody, the amount of Nav1.4 at the plasma membrane was increaseed by CaM and CaM1234. Mutation in the IQ motif increased the Na+ current and recovery rates. CaM had a similar effect in enhancing the Nav1.1 currents. These findings suggest that CaM modulates VGSCs via the IQ motif in response to intracellular calcium concentration changes. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T23:29:47Z (GMT). No. of bitstreams: 1 ntu-101-R99b41001-1.pdf: 5275715 bytes, checksum: ef697f69dc72d43858c54b5ca1a4a905 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii 英文摘要 iii 1. Introduction 1 1.1 Voltage-gated sodium channel (VGSC) and action potentials 1 1.2 The structure of voltage-gated sodium channels (VGSCs) 3 1.3 The ion permeation selectivity of VGSCs 4 1.4 The voltage-dependent activation of VGSCs 5 1.5 The tissue distribution of voltage-gated sodium channels (VGSCs) 5 1.6 Calmodulin 7 1.7 IQ motif 8 1.8 Channelopathies caused by Nav1.4 and Nav1.1 dysfunction 11 1.9 Whole-cell voltage clamp recordings 13 2. Materials and Methods 15 2.1 Plasmids 15 2.2 Primer designs and site-directed mutagenesis reaction 15 2.3 Competent cells preparation 16 2.4 Transformation 17 2.5 Plasmid DNA preparation 17 2.6 293T cell culture 18 2.7 Transfection 18 2.8 Electrophysiology 19 2.9 Pipette solution 21 2.10 Bath buffer (normal Na+) 21 2.11 Immunofluorescence staining 21 2.12 Western blot analysis 22 2.13 Data analysis 23 3. Results 24 3.1 The construction of sodium channel IQ motif mutants 24 3.2 CaM enhances Nav1.4 currents in 293T cells 24 3.3 CaM and CaM1234 enhance Nav1.4 plasma membrane localization 26 3.4 CaM and CaM1234 enhance the membrane localization Nav1.4 by Western blot analysis 27 3.5 Intracellular Ca2+ inhibits Na+ currents in the absence of CaM 27 3.6 CaM further enhances Na+ currents in the presence of Ca2+ 28 3.7 CaM1234 with impaired Ca2+ binding ability has no effect on Na+ currents 29 3.8 Nav1.4 IQ/IA exhibits smaller Na+ current amplitudes and slower recovery from inactivation 31 4. Discussion 32 4.1 Three latent regions involve in the modulation of VGSCs function 33 4.2 Functional effects of Ca2+-binding ability of CaM 34 4.3 EF-hand Ca2+ binding affinity might alter VGSC inactivation properties 34 4.4 IQ motif mutations majorly affect VGSCs recovery rates 35 4.5 Na+ current influx and skeletal muscle function 35 4.6 Impaired CaM-IQ motif interaction and channelopathies 36 5. Table 39 6. Scheme 45 7. Figure 46 Reference 67 | |
dc.language.iso | en | |
dc.title | 鈣調素對電壓依賴型鈉離子通道的調控之研究 | zh_TW |
dc.title | The Modulation Effects of Calmodulin on
Voltage-gated sodium channels | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 湯志永(Chih-Yung Tang),謝如姬(Ru-Chi Shieh),黃榮棋(Rong-Chi Huang) | |
dc.subject.keyword | 鈣調素,鈣離子,IQ motif構造,鈉離子通道Nav1.4,電壓依賴型鈉離子通道, | zh_TW |
dc.subject.keyword | calmodulin,Ca2+,IQ motif,Nav1.4,voltage-gated sodium channels, | en |
dc.relation.page | 80 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-07-30 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 動物學研究所 | zh_TW |
顯示於系所單位: | 動物學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-101-1.pdf 目前未授權公開取用 | 5.15 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。