MULTIFRACTAL CHARACTERISTICS OF THE MITOCHONDRIAL BK CHANNEL ACTIVITY IN THE PRESENCE OF THE CHANNEL-ACTIVATING FLAVONOIDS

Fractals Pub Date : 2024-07-06 DOI:10.1142/s0218348x24501019
P. Trybek, Ł. Machura, Piotr Bednarczyk, Urszula Cojg, Patrycja Podleśny, Kamila Szumała, Agata WAWRZKIEWICZ-JAŁOWIECKA
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Abstract

Over the years, the (multi)fractal nature of signals describing the activity of ion channels has been observed both at the level of single-channel currents and the temporal scaling of the corresponding sojourns in conducting and non-conducting states. The recognized nonlinear and self-similar properties were interpreted regarding the underlying channel gating machinery. Nevertheless, the literature lacks in (multi)fractal description of the biochemical stimulation of ion channels. Therefore, in this work, we provide a multifractal description of the effects exerted by two different flavonoids — naringenin (Nar) and quercetin (Que) — being the regulators of the large-conductance voltage- and Ca[Formula: see text]-activated K[Formula: see text] channels from the inner mitochondrial membrane (mitoBK). Toward this aim, the focus-based multifractal detrended fluctuation analysis (MFDFA) was applied to the patch-clamp data obtained in the presence of Nar and Que in micromolar concentrations and the corresponding controls. Our results show that mitoBK channel activity has well-pronounced multifractal characteristics and long-range memory (measured by the generalized Hurst exponent) under biochemical stimulation by Nar and Que and in the absence of these substances. The spectral properties significantly change after the randomization of the analyzed series. Therefore, multifractality is an inherent feature of the mitoBK channel currents, which stems from their statistical distribution and temporal organization. Both flavonoids have similar structures and exert channel-activating effects, but they differently affect the parameters of the multifractal spectra of the corresponding patch-clamp signals. Coordination of Que leads to more prominent changes in signal complexity than Nar at membrane hyper- and depolarization. It suggests that this flavonoid has a stronger impact on the conformational dynamics of the mitoBK channels in comparison with naringenin.
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线粒体 bk 通道活性在通道激活类黄酮存在下的多分形特征
多年来,无论是在单通道电流层面,还是在传导和非传导状态下相应的时间缩放层面,都观察到了描述离子通道活动信号的(多)分形性质。公认的非线性和自相似特性被解释为潜在的通道门控机制。然而,文献缺乏对离子通道生化刺激的(多)分形描述。因此,在这项工作中,我们对两种不同的类黄酮--柚皮苷(Nar)和槲皮素(Que)--作为线粒体内膜(mitoBK)大电导电压和钙[式:见正文]激活 K[式:见正文]通道的调节剂所产生的影响进行了多分形描述。为此,我们将基于聚焦的多分形去趋势波动分析(MFDFA)应用于在微摩尔浓度的 Nar 和 Que 存在下获得的贴片钳数据以及相应的对照组。结果表明,在Nar和Que的生化刺激下,以及在没有这两种物质的情况下,线粒体BK通道活动具有明显的多分形特征和长程记忆(通过广义赫斯特指数测量)。在对分析序列进行随机化处理后,光谱特性会发生明显变化。因此,多折射性是线粒体BK通道电流的固有特征,源于其统计分布和时间组织。这两种黄酮类化合物具有相似的结构,并具有激活通道的作用,但它们对相应的贴片钳信号的多分形光谱参数的影响却不同。在膜超极化和去极化时,阙协调导致的信号复杂性变化比 Nar 更为突出。这表明,与柚皮苷相比,阙黄酮对线粒体BK通道构象动力学的影响更大。
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