Department of Physical Chemistry and Technology of Polymers, Faculty of Chemistry, Silesian University of Technology, Gliwice, 44-100, Poland.
Faculty of Science and Technology, University of Silesia in Katowice, Chorzow, 41-500, Poland.
Biosystems. 2021 Jan;199:104310. doi: 10.1016/j.biosystems.2020.104310. Epub 2020 Nov 25.
Mitochondrial large-conductance voltage- and Ca-activated potassium channels (mitoBK) exhibit substantial similarities in their physiology regardless of the channel's location. Nevertheless, depending on the cell type, composition of membranes can vary, and mitoBK channels can be expressed in different splice variants as well as they can be co-assembled with different types of auxiliary β subunits. These factors can modulate their voltage- and Ca-sensitivity, and single-channel current kinetics. It is still an open question to what extent the mentioned factors can affect the complexity of the conformational dynamics of the mitoBK channel gating. In this work the dynamical diversity of mitoBK channels from different cell types was unraveled by the use of nonlinear methods of analysis: multifractal detrended fluctuation analysis (MFDFA) and multiscale entropy (MSE). These techniques were applied to the experimental series of single channel currents. It turns out that the differences in the mitoBK expression systems influence gating machinery by changing the scheme of switching between the stable channel conformations, and affecting the average number of available channel conformations (this effect is visible for mitoBK channels in glioblastoma cells). The obtained results suggest also that a pathological dynamics can be represented by signals of relatively low complexity (low MSE of the mitoBK channel gating in glioblastoma).
线粒体大电导电压和 Ca 激活钾通道(mitoBK)在生理学上具有显著的相似性,而不论通道的位置如何。然而,根据细胞类型的不同,膜的组成可以有所不同,而且 mitoBK 通道可以以不同的剪接变体表达,也可以与不同类型的辅助β亚基共同组装。这些因素可以调节它们的电压和 Ca 敏感性以及单通道电流动力学。到什么程度,上述因素可以影响 mitoBK 通道门控的构象动力学的复杂性,这仍然是一个悬而未决的问题。在这项工作中,通过使用非线性分析方法:多重分形去趋势波动分析(MFDFA)和多标度熵(MSE),揭示了来自不同细胞类型的 mitoBK 通道的动力学多样性。这些技术应用于单通道电流的实验系列。事实证明,mitoBK 表达系统的差异通过改变稳定通道构象之间的切换方案,以及影响可用通道构象的平均数量来影响门控机制(这种影响对于神经胶质瘤细胞中的 mitoBK 通道可见)。所得结果还表明,病理动力学可以由相对低复杂度的信号表示(神经胶质瘤中 mitoBK 通道门控的低 MSE)。