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钾离子通道作为细胞中阳离子浓度的调节器之一, 在神经细胞动作电位去极化及复极化过程中起着重要作用. KcsA(K+ conduction and selectivity architecture)通道结构简单又具有钾离子通道的共性, 常作为钾通道研究的模板. 本文采用布朗动力学数值方法, 系统地对KcsA钾通道的电学特性进行模拟. 得到静电场作用下通道内离子的平均势能分布、均匀与非均匀溶液的电流-电压特性曲线、通道轴向的离子浓度分布曲线以及电导-浓度曲线. 研究结果发现, KcsA钾离子通道选择性过滤区域几乎完全阻隔了Cl–通过, 呈现倾向于K+通过的特异选择特性; 其电流-电压曲线基本呈线性分布, 电导-浓度曲线呈现先增大后平缓的趋势, 基本规律与实验现象一致. 另外, 还模拟分析了太赫兹场对通道K+电流的影响, 相比于仅施加同幅值静电场, 选定的0.6 THz, 1.2 THz, 5 THz的太赫兹场可通过影响离子对之间的相互作用势能, 降低通道平均力势, 从而增大K+电流. 本文的研究不但加深了对于KcsA钾离子通道的规律性认识, 还为其他类型离子通道以及太赫兹场对离子通道特性影响的研究提供了新思路.As one of the regulators of cationic concentration in cells, potassium channels play an important role in the depolarization and repolarization of nerve cell. KcsA (K+ conduction and selectivity architecture) channel is simple and has the commonness of potassium ion channel, which is often used as a template for potassium channel research. In this paper, Brownian dynamics (BD) method is used to simulate the electrical characteristics of the actual KcsA potassium channel systematically. The potential mean force (PMF) of ions in the channel under electrostatic field, the current-voltage characteristic curve of symmetric solution and asymmetric solution, the ion concentration distribution curve in the axial direction of the channel, and the conduction-concentration curve are obtained. The results show that the selectivity filter region of KcsA potassium channel blocks the passage of Cl– basically, showing a special selection characteristic of the passage of K+, that its current-voltage curve presents a basically linear distribution, and that the conductivity-concentration curve presents a trend of first increasing and then flattening. The basic characteristic is consistent with the experimental phenomenon. In addition, the influence of the THz field on the channel K+ current is also simulated and analyzed. Compared with applying only the same amplitude electrostatic field, the selected terahertz field of 0.6 THz, 1.2 THz, and 5 THz can reduce the PMF by affecting the interaction potential energy between ion pairs, thereby increasing the K+ current. The research in this paper not only deepens the understanding of the regularity of KcsA potassium ion channels, but also provides a new idea for studying other types of ion channels and the influence of terahertz field on the characteristics of ion channels.
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Keywords:
- Brownian dynamics /
- KcsA potassium ion channel /
- potential of mean force /
- terahertz field
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图 1 KcsA钾离子通道结构 (a)侧视图; (b)俯视图
Fig. 1. KcsA potassium ion channel structure: (a) Side view; (b) top view.
图 4 KcsA通道轴向K+和Cl–的一维PMF分布
Fig. 4. One-dimensional PMF distribution of K+ and Cl– in axial direction of KcsA channel.
图 5 KcsA钾离子通道I-V特性曲线 (a)均匀溶液; (b)非均匀溶液
Fig. 5. I-V characteristic curve of KcsA potassium ion channel: (a) Symmetric solution; (b) asymmetric solution.
图 6 (a)均匀溶液下轴向离子浓度分布; (b)某一时刻离子空间分布
Fig. 6. (a) Axial ion concentration distribution in symmetric solution; (b) spatial distribution of ions at a certain time.
图 7 非均匀溶液下轴向离子浓度分布 (a) 0.1 mol/L∶1.0 mol/L; (b) 1.0 mol/L∶0.1 mol/L
Fig. 7. Axial ion concentration distribution in asymmetric solution: (a) 0.1 mol/L∶1.0 mol/L; (b) 1.0 mol/L∶0.1 mol/L
图 8 (a) G-c分布; (b) 规范化后的离子电导G/c-c曲线
Fig. 8. (a) G-c distribution; (b) normalized ionic conductivity G/c-c curve.
图 9 不同频率太赫兹场作用下通道的(a) K+电流和(b)平均力势
Fig. 9. (a) The K+ current and (b) the PMF inside the channel under the THz field at different frequencies.
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[1] Breedlove S M, Watson N V 2017 Behavioral Neuroscience (8th Ed.) (Sunderland, Massachusetts: Sinauer Associates, Inc) pp29,30
[2] Maffeo C, Bhattacharya S, Yoo J, Wells D, Aksimentiev A 2012 Chem. Rev. 112 6250
Google Scholar
[3] Corry B, Chung S H 2006 Cell. Mol. Life. Sci. 63 301
Google Scholar
[4] Tu B, Bai S Y, Chen M X, Xie Y, Zhang L B, Lu B Z 2014 Comput. Sci. Discov. 7 014002
Google Scholar
[5] Im W, Roux B 2002 J. Mol. Biol. 322 851
Google Scholar
[6] Im W, Seefeld S, Roux B 2000 Biophys. J. 79 788
Google Scholar
[7] Lee K I, Jo S, Rui H, Egwolf B, Roux B, Pastor R W, Im W 2012 J. Comput. Chem. 33 331
Google Scholar
[8] Chung S H, Hoyles M, Allen T, Kuyucak S 1998 Biophys. J. 75 793
Google Scholar
[9] Noskov S Y, Im W, Roux B 2004 Biophys. J. 87 2299
Google Scholar
[10] Kutzner C, Grubmüller H, Groot B L, Zachariae U 2011 Biophys. J. 101 755
Google Scholar
[11] Lee K I, Rui H, Pastor R W, Im W 2011 Biophys. J. 100 611
Google Scholar
[12] Boiteux C, Kraszewski S, Ramseyer C, Girardet C 2007 J. Mol. Model. 13 699
Google Scholar
[13] Allen T W, Chung S H 2001 Biochim. Biophys. Acta 1515 83
Google Scholar
[14] Chung S H, Allen T W, Kuyucak S 2002 Biophys. J. 82 628
Google Scholar
[15] Chung S H, Allen T W, Kuyucak S 2002 Biophys. J. 83 263
Google Scholar
[16] Allen T W, Kuyucak S, Chung S H 2000 Biophys. Chem. 86 1
Google Scholar
[17] Jiang Y X, Lee A, Chen J Y, Cadene M, Chait B T, MacKinnon R 2002 Nature 417 523
Google Scholar
[18] Sansoma M S P, Shrivastavab I H, Brighta J N, Tatec J, Capenera C E, Biggin P C 2002 Biochim. Biophys. Acta. 1565 294
Google Scholar
[19] Horng T L, Chen R S, Leonardi M V, Franciolini F, Catacuzzeno L 2022 Front. Mol. Biosci. 9 1
Google Scholar
[20] Li S C, Hoyles M, Kuyucak S, Chung S H 1998 Biophys. J. 74 37
Google Scholar
[21] Chung S H, AllenT W, Hoyles M, Kuyucak S 1999 Biophys. J. 77 2517
Google Scholar
[22] Hoyles M, Kuyucak S, Chung S H 1998 Phys. Rev. E. 58 3654
Google Scholar
[23] Schirmer T, Phale P S 1999 J. Mol. Biol. 294 1159
Google Scholar
[24] Sunhwan J, Taehoon K, Iyer V G, Jo S, Kim T, Iyer V G, Im W 2008 J. Comput. Chem. 29 1859
Google Scholar
[25] Im W, Roux B 2001 J. Chem. Phys. 115 4850
Google Scholar
[26] Berti C, Furini S, Gillespie D, Boda D, Eisenberg R S, Sangiorgi E, Fiegna C 2014 J. Chem. Theory. Comput. 10 2911
Google Scholar
[27] Lemasurier M, Heginbotham L, Miller C 2001 J. Gen. Physiol. 118 303
Google Scholar
[28] 薄文斐 2020 博士学位论文 (成都: 电子科技大学)
Bo W F 2020 Ph. D. Dissertation (Chengdu: University of Electronic Science and Technology of China) (in Chinese)
[29] Dalzell D R, McQuade J, Vincelette R, Ibey B, Payne J, Thomas R, Roach W P, Roth C L, Wilmink G J 2010 Proc. SPIE 7562 75620M
Google Scholar
[30] Wei C, Zhang Y C, Li R, Wang S G, Wang T, Liu J H, Liu Z, Wang K J, Liu J S, Liu X M 2018 Biomed. Opt. Express 9 3998
Google Scholar
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