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標題: | 鈉離子通道不活化閘門與S4/D4區段可能之交互作用 The Possibility of Interaction between Inactivation Gate and S4/D4 Segment in Sodium Channel |
作者: | Yu-Dian Chen 陳昱典 |
指導教授: | 郭鐘金(Chung-Chin Kuo) |
關鍵字: | 不活化閘門,S4/D4區段, inactivation gate,S4/D4 segment, |
出版年 : | 2009 |
學位: | 碩士 |
摘要: | 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。 Na+ 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45474 |
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