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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45474
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor郭鐘金(Chung-Chin Kuo)
dc.contributor.authorYu-Dian Chenen
dc.contributor.author陳昱典zh_TW
dc.date.accessioned2021-06-15T04:22:10Z-
dc.date.available2015-03-12
dc.date.copyright2010-03-12
dc.date.issued2009
dc.date.submitted2009-10-12
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McPhee, J.C., D.S. Ragsdale, T. Scheuer, and W.A. Catterall. 1994. A mutation in segment IVS6 disrupts fast inactivation of sodium channels. Proceedings of
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the National Academy of Sciences of the United States of America. 91:12346-12350. McPhee, J.C., D.S. Ragsdale, T. Scheuer, and W.A. Catterall. 1995. A Critical Role for Transmembrane Segment IVS6 of the Sodium Channel [IMAGE] Subunit in Fast Inactivation. J. Biol. Chem. 270:12025-12034. McPhee, J.C., D.S. Ragsdale, T. Scheuer, and W.A. Catterall. 1998. A critical role for the S4-S5 intracellular loop in domain IV of the sodium channel alpha-subunit in fast inactivation. J Biol Chem. 273:1121-1129. Mitrovic, N., A.L. George, Jr., and R. Horn. 2000. Role of domain 4 in sodium channel slow inactivation. J Gen Physiol. 115:707-718. Noceti, F., P. Baldelli, X. Wei, N. Qin, L. Toro, L. Birnbaumer, and E. Stefani. 1996. Effective gating charges per channel in voltage-dependent K+ and Ca2+ channels. J Gen Physiol. 108:143-155. Noda, M., S. Shimizu, T. Tanabe, T. Takai, T. Kayano, T. Ikeda, H. Takahashi, H. Nakayama, Y. Kanaoka, N. Minamino, K. Kangawa, H. Matsuo, M.A. Raftery, T. Hirose, S. Inayama, H. Hayashida, T. Miyata, and S. Numa. 1984. Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature. 312:121-127. Nonner, W. 1980. Relations between the inactivation of sodium channels and the immobilization of gating charge in frog myelinated nerve. The Journal of Physiology. 299:573-603. O'Reilly, J.P., S.Y. Wang, and G.K. Wang. 2000. A point mutation in domain 4-segment 6 of the skeletal muscle sodium channel produces an atypical inactivation state. Biophys J. 78:773-784. Papazian, D.M., X.M. Shao, S.A. Seoh, A.F. Mock, Y. Huang, and D.H. Wainstock. 1995. Electrostatic interactions of S4 voltage sensor in Shaker K+ channel. Neuron. 14:1293-1301. Patlak, J. 1991. Molecular kinetics of voltage-dependent Na+ channels. Physiol Rev. 71:1047-1080. Perozo, E. 1992. Gating currents in Shaker K+ channels. Implications for activation and inactivation models. Biophysical Journal. 62:160. Rohl, C.A., F.A. Boeckman, C. Baker, T. Scheuer, W.A. Catterall, and R.E. Klevit. 1999. Solution structure of the sodium channel inactivation gate. Biochemistry. Scheuer, T., V.J. Auld, S. Boyd, J. Offord, R. Dunn, and W.A. Catterall. 1990. Functional properties of rat brain sodium channels expressed in a somatic cell line. Science. 247:854-858.
Schonherr, R., L.M. Mannuzzu, E.Y. Isacoff, and S.H. Heinemann. 2002. Conformational switch between slow and fast gating modes: allosteric
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regulation of voltage sensor mobility in the EAG K+ channel. Neuron. 35:935-949.. Schoppa, N.E., K. McCormack, M.A. Tanouye, and F.J. Sigworth. 1992. The size of gating charge in wild-type and mutant Shaker potassium channels. Science. 255:1712-1715. Seoh, S.A., D. Sigg, D.M. Papazian, and F. Bezanilla. 1996. Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel. Neuron. 16:1159-1167. Shih, T.M., and A.L. Goldin. 1997. Topology of the Shaker Potassium Channel Probed with Hydrophilic Epitope Insertions. J. Cell Biol. 136:1037-1045. Sirota, F.L. 2002. Molecular modeling and dynamics of the sodium channel inactivation gate. Biophysical Journal. 82:1207. Smith, M.R., and A.L. Goldin. 1997. Interaction between the sodium channel inactivation linker and domain III S4-S5. Biophys J. 73:1885-1895. Solaro, C.R., and C.J. Lingle. 1992. Trypsin-sensitive, rapid inactivation of a calcium-activated potassium channel. Science. 257:1694-1698. Starace, D.M., and F. Bezanilla. 2001. Histidine scanning mutagenesis of basic residues of the S4 segment of the shaker k+ channel. J Gen Physiol. 117:469-490. Starace, D.M., and F. Bezanilla. 2004. A proton pore in a potassium channel voltage sensor reveals a focused electric field. Nature. 427:548-553. Stimers, J.R., F. Bezanilla, and R.E. Taylor. 1985. Sodium channel activation in the squid giant axon. Steady state properties. J Gen Physiol. 85:65-82. Stuhmer, W., F. Conti, H. Suzuki, X. Wang, M. Noda, N. Yahagi, H. Kubo, and S. Numa. 1989. Structural parts involved in activation and inactivation of the sodium channel. Nature. 339:597-603. Tiwari-Woodruff, S.K. 1997. Electrostatic interactions between transmembrane segments mediate folding of Shaker K+ channel subunits. Biophysical Journal. 72:1489. Tiwari-Woodruff, S.K., M.A. Lin, C.T. Schulteis, and D.M. Papazian. 2000. Voltage-dependent structural interactions in the Shaker K(+) channel. J Gen Physiol. 115:123-138. Vassilev, P., T. Scheuer, and W.A. Catterall. 1989. Inhibition of inactivation of single sodium channels by a site-directed antibody. Proc Natl Acad Sci U S A. 86:8147-8151. Vassilev, P.M., T. Scheuer, and W.A. Catterall. 1988. Identification of an intracellular peptide segment involved in sodium channel inactivation. Science. 241:1658-1661.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45474-
dc.description.abstract鈉離子通道是普遍存在於興奮性細胞的電位依賴性離子通道,此通道固有性質在於能有效感應膜電位改變並改變結構讓鈉離子通透,並以自發性進入不活化態的方式來調節離子流量。多年來眾多研究已經證實鈉離子通道的活化現象和不活化現象是偶合在一起的,而不活化現象也已經證實和通道的S4/D4(第四單元之第四穿膜區段)有密切相關。然而,負責發動不活化現象的不活化閘門和S4/D4是否存在著交互作用卻鮮有研究。本研究藉著在大鼠腦ⅡA型鈉離子通道的S4/D4上”R+1”軸線、”R-1”軸線上的疏水性胺基酸和D3-4linker (Domain 3和Domain 4的連接區段)上I1488、F1489位置之間用點突變的技術來探討去極化過程中S4/D4不同軸線之間和不活化閘門可能的交互作用。我們將S4/D4上F1625、I1628位置和I1488、F1489位置做相反電性配對之後,通道的不活化曲線與單突變的和相較出現明顯的變化。而將S4/D4上R1、R2上下的V1627、L1630位置和I1488、F1489位置配對後,通道的活化速率明顯減慢;其中L1630位置的效應大於V1627,F1489搭配的效果大於I1488的效果。而I1488、F1489位置和F1625、V1627、I1628、L1630、G1642位置搭配的結果則觀察到通道不活化速率有稍微變快的現象。而與I1633、I1636、L1639、I1640位置配對後,則普遍觀察到不活化速率減慢的情況。我們認為D3-4linker在通道處於休息態時的空間位置似乎可能接近S4/D4上V1627、L1630位置;而S4/D4上I1633~I1640若干位置似乎可能在通道活化過程中參與了不活化受體的形成。總結而言,我們認為鈉離子通道的S4/D4可能經由與I1488、F1489之互動,而影響不活化閘門之開關外,似乎也可能因而參與了通道活化-不活化的偶合過程。zh_TW
dc.description.abstractNa+ channel is one of voltage-dependent ion channel family and commonly exists in the excitable cell, which inherently possess the ability of effectively sensing the change of membrane voltage and changing its structure for Na+ ion to permeate, then regulate ion flux by spontaneously enter the inactivation state .A number of researches have indicated that activation and inactivation are coupled actions, and inactivation has been proven to be closely related to the S4/D4 of Na+ channel. However, whether there are interactions between the presumable inactivation gate D3-4linker (the linker between domain 3 and domain 4) and S4/D4 (the fourth transmembrane segment of domain 4) remains unclear. With the technique of point mutation between the hydrophobic residues on both “R+1” and “R-1” axis in S4/D4 of the rat brain type IIA Na+ channel, and the position I1488 and F1489 on D3-4linker,We try to investigate the possible interactions between the foregoing structure . We found that after making a counter charge pair of the mutations that between F1625、I1628 and I1488、F1489,the change of inactivation curve between double mutant and the sum of single mutants is different . Besides, after making a counter charge pair of the mutations that between V1627、L1630 and I1488、F1489, the activation rate of the channel apparently slows down. Moreover, making counter charge pair with F1625、V1627、I1628、L1630、G1642,the inactivation rate of the channel increases. On the other hand, making counter charge pair with I1633、I636、L1639、I1640, the inactivation rate of the channel slows down. We considered that D3-4linker may be close to V1627、L1630 in S4/D4 at resting state of channel, and several sites between I1633~I1640 may be involved in formation of inactivation gate receptor while channel is in activation process. The study result shows that S4/D4 may interact with I1488 and F1489 not only to make sodium channel inactivation, but
3
also to contribute to the mechanisms coupling activation and inactivation.
en
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en
dc.description.tableofcontents中文摘要...........................................................1
英文摘要...........................................................2
第一章 導論…………………………………………………………………………4
第二章 材料與方法……………………………………………………………….17
第三章 結果……………………………………………………………………….21
第四章 討論……………………………………………………………………….29
圖次
圖一 電位開關性鈉離子通道結構圖…………………………………………40
圖二 WT,I1488E,F1489E 的電流記錄與活化曲線………………………….41
圖三 WT,I1488E,F1489E之電流記錄與不活化曲線……………………… 42
圖四 I1488E和S4/D4上的”R-1”軸線各個疏水性胺機酸之Arginine突變配對之活化曲線圖 …………………………………………………….43
圖五 I1488E和S4/D4上的”R-1”軸線各個疏水性胺基酸之Arginine突變配對之不活化曲線圖……………………………………………......44
圖六 I1488E和S4/D4上的”R+1”軸線各個疏水性胺基酸之Arginine突變配對活化曲線圖………………………………………………………..45
圖七 I1488E和S4/D4上的”R+1”軸線各個疏水性胺基酸之Arginine突變配對不活化曲線圖……………………………………………………..46
圖八 F1489E和S4/D4上的”R-1”軸線各個疏水性胺基酸之Arginine突變配對之活化曲線圖………………………………………………………47
圖九 F1489E和S4/D4上的”R-1”軸線各個疏水性胺基酸之Arginine突變配對之不活化曲線圖…………………………………………………..48
圖十 F1489E和S4/D4上的”R+1”軸線各個疏水性胺基酸之Arginine突變配對之活化曲線圖………………………………………………………49
圖十一 F1489E和S4/D4上的”R+1”軸線各個疏水性胺基酸之Arginine突變配對之不活化曲線圖……………………………………………………50
圖十二 I1488E和S4/D4上的”R-1”軸線各個疏水性胺基酸之Arginine突變配對之活化速率比較圖………………………………………………..51
圖十三 I1488E和S4/D4上的”R-1”軸線各個疏水性胺基酸之Arginine突變配對之不活化速率與比例比較圖……………………………………..52
圖十四 I1488E和S4/D4上的”R+1”軸線各個疏水性胺基酸之Arginine突變配對之活化速率比較圖………………………………………………..53
圖十五 I1488E和S4/D4上的”R+1”軸線各個疏水性胺基酸之Arginine突變配對之不活化速率與比例比較圖……………………………………..54
圖十六 F1489E和S4/D4上的”R-1”軸線各個疏水性胺基酸之Arginine突變配對之活化速率曲線圖………………………………………………..55
圖十七 F1489E和S4/D4上的”R-1”軸線各個疏水性胺基酸之Arginine突變配對之不活化速率和比例圖……………………………………………56
圖十八 F1489E和S4/D4上的”R+1”軸線各個疏水性胺基酸之Arginine突變配對之活化速率曲線圖…………………………………………………57
圖十九 F1489E和S4/D4上的”R+1”軸線各個疏水性胺基酸之Arginine突變配對之不活化速率和比例圖…………………………………………..58
參考文獻…………………………………………………………………………..59
dc.language.isozh-TW
dc.title鈉離子通道不活化閘門與S4/D4區段可能之交互作用zh_TW
dc.titleThe Possibility of Interaction between Inactivation Gate and S4/D4 Segment in Sodium Channelen
dc.typeThesis
dc.date.schoolyear98-1
dc.description.degree碩士
dc.contributor.oralexamcommittee楊雅晴,黃榮棋
dc.subject.keyword不活化閘門,S4/D4區段,zh_TW
dc.subject.keywordinactivation gate,S4/D4 segment,en
dc.relation.page64
dc.rights.note有償授權
dc.date.accepted2009-10-12
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept生理學研究所zh_TW
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