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通过短程和长程相关性分析揭示人胶质母细胞瘤细胞中细胞和线粒体膜 BK 通道门控动力学的差异。

Differences in Gating Dynamics of BK Channels in Cellular and Mitochondrial Membranes from Human Glioblastoma Cells Unraveled by Short- and Long-Range Correlations Analysis.

机构信息

Department of Physical Chemistry and Technology of Polymers, Silesian University of Technology, 44-100 Gliwice, Poland.

Faculty of Science and Technology, University of Silesia in Katowice, 41-500 Chorzow, Poland.

出版信息

Cells. 2020 Oct 15;9(10):2305. doi: 10.3390/cells9102305.

DOI:10.3390/cells9102305
PMID:33076484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7602617/
Abstract

The large-conductance voltage- and Ca2+-activated K+ channels (BK) are encoded in humans by the Kcnma1 gene. Nevertheless, BK channel isoforms in different locations can exhibit functional heterogeneity mainly due to the alternative splicing during the Kcnma1 gene transcription. Here, we would like to examine the existence of dynamic diversity of BK channels from the inner mitochondrial and cellular membrane from human glioblastoma (U-87 MG). Not only the standard characteristics of the spontaneous switching between the functional states of the channel is discussed, but we put a special emphasis on the presence and strength of correlations within the signal describing the single-channel activity. The considered short- and long-range memory effects are here analyzed as they can be interpreted in terms of the complexity of the switching mechanism between stable conformational states of the channel. We calculate the dependencies of mean dwell-times of (conducting/non-conducting) states on the duration of the previous state, Hurst exponents by the rescaled range R/S method and detrended fluctuation analysis (DFA), and use the multifractal extension of the DFA (MFDFA) for the series describing single-channel activity. The obtained results unraveled statistically significant diversity in gating machinery between the mitochondrial and cellular BK channels.

摘要

大电导电压和 Ca2+激活的钾通道(BK)在人类中由 Kcnma1 基因编码。然而,不同位置的 BK 通道同工型由于 Kcnma1 基因转录过程中的选择性剪接,主要表现出功能异质性。在这里,我们希望从人胶质母细胞瘤(U-87 MG)的线粒体和细胞膜内来研究 BK 通道的动态多样性的存在。我们不仅讨论了通道功能状态之间自发切换的标准特征,而且特别强调了描述单通道活动的信号内相关性的存在和强度。这里分析了考虑的短程和远程记忆效应,因为它们可以根据通道稳定构象状态之间的切换机制的复杂性来解释。我们通过重标极差 R/S 方法和去趋势波动分析(DFA)计算了(导通/非导通)状态的平均停留时间对前一个状态持续时间的依赖性,并使用单通道活动描述序列的多重分形扩展 DFA(MFDFA)。所得到的结果揭示了线粒体和细胞 BK 通道门控机制之间在统计学上显著的多样性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/0f94c83bae4c/cells-09-02305-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/cb29b942e7bc/cells-09-02305-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/940422ed4a2f/cells-09-02305-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/e39b8837f5d0/cells-09-02305-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/5a60c42fe1f1/cells-09-02305-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/549a5d46cc32/cells-09-02305-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/5136f9f2417e/cells-09-02305-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/b35a5fb28f9f/cells-09-02305-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/0f94c83bae4c/cells-09-02305-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/cb29b942e7bc/cells-09-02305-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/940422ed4a2f/cells-09-02305-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/e39b8837f5d0/cells-09-02305-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/5a60c42fe1f1/cells-09-02305-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/549a5d46cc32/cells-09-02305-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/5136f9f2417e/cells-09-02305-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/b35a5fb28f9f/cells-09-02305-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1f/7602617/0f94c83bae4c/cells-09-02305-g008.jpg

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