In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17$\alpha$-hydroxylase), 3$\beta$-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.

Potassium channels are widely distributed integral proteins responsible for the effective and selective transport of $K^{+}$ ions through the biological membranes. According to the existing structural and mechanistic differences, they are divided into several groups. All of them are considered important molecular drug targets due to their physiological roles, including the regulation of membrane potential or cell signaling. One of the recent trends in molecular pharmacology is the evaluation of the therapeutic potential of natural compounds and their derivatives, which can exhibit high specificity and effectiveness. Among the pharmaceuticals of plant origin, which are potassium channel modulators, flavonoids appear as a powerful group of biologically active substances. It is caused by their well-documented anti-oxidative, anti-inflammatory, anti-mutagenic, anti-carcinogenic, and antidiabetic effects on human health. Here, we focus on presenting the current state of knowledge about the possibilities of modulation of particular types of potassium channels by different flavonoids. Additionally, the biological meaning of the flavonoid-mediated changes in the activity of $K^{+}$ channels will be outlined. Finally, novel promising directions for further research in this area will be proposed.

Potassium channels play an important physiological role in glioma cells. In particular, voltage- and Ca2+-activated large-conductance BK channels (gBK in gliomas) are involved in intensive growth and extensive migrating behavior of the mentioned tumor cells, thus, they may be considered as a drug target in therapeutic treatment of glioblastoma. To enable appropriate drug design, molecular mechanisms of gBK channel activation by diverse stimuli should be unraveled, as well as the way that the specific conformational states of the channel relates to its functional properties (conducting/non-conducting). There is an open debate about the actual mechanism of BK channel gating, including the question of how the channel proteins undergo a range of conformational transitions when they flicker between non-conducting (functionally closed) and conducting (open) states. The details of channel conformational diffusion ought to have its representation in the properties of the experimental signal which describes the ion channel activity. Non-linear methods of analysis of experimental non-stationary series can be useful for observing the changes in the number of channel substates available from a geometrical and energetic point of view at given external conditions. In this work we analyze whether multifractal properties of activity of glioblastoma BK channels depend on membrane potential, and which states, conducting or nonconducting, affect the total signal to the larger extent. In this aim we carried out patch-clamp experiments at different levels of membrane hyper- and depolarization. The obtained time series of single channel currents were analyzed by the use of the Multifractal Detrended Fluctuation Analysis (MFDFA) method in a standard form and incorporating focus-based multifractal (FMF) formalism. Thus, we show the applicability of a modified MFDFA technique in analysis of an experimental patch clamp time series. The obtained results suggest that membrane potential strongly affects conformational space of the gBK channel proteins and the considered process has non-linear multifractal characteristics. These properties are inherent features of analyzed signals due to the fact that main tendencies vanish after shuffling the data.

Potassium channels emerge as one of the crucial groups of proteins that shape the biology of cancer cells. Their involvement in processes like cell growth, migration, or electric signaling, seems obvious. However, the relationship between the function of $K^{+}$ channels, glucose metabolism, and cancer glycome appears much more intriguing. Among the typical hallmarks of cancer, one can mention the switch to aerobic glycolysis as the most favorable mechanism for glucose metabolism and glycome alterations. This review outlines the interconnections between the expression and activity of potassium channels, carbohydrate metabolism, and altered glycosylation in cancer cells, which have not been broadly discussed in the literature hitherto. Moreover, we propose the potential mediators for the described relations (e.g., enzymes, microRNAs) and the novel promising directions (e.g., glycans-orinented drugs) for further research.

BK channels are potassium selective and exhibit large single-channel conductance. They play an important physiological role in glioma cells: they are involved in cell growth and extensive migrating behavior. Due to the fact that these processes are accompanied by changes in membrane stress, here, we examine mechanosensitive properties of BK channels from human glioblastoma cells (gBK channels). Experiments were performed by the use of patch-clamp method on excised patches under membrane suction (0–40 mmHg) at membrane hyper- and depolarization. We have also checked whether channel’s activity is affected by possible changes of membrane morphology after a series of long impulses of suction. Unconventionally, we also analyzed internal structure of the experimental signal to make inferences about conformational dynamics of the channel in stressed membranes. We examined the fractal long-range memory effect (by R/S Hurst analysis), the rate of changes in information by sample entropy, or correlation dimension, and characterize its complexity over a range of scales by the use of Multiscale Entropy method. The obtained results indicate that gBK channels are mechanosensitive at membrane depolarization and hyperpolarization. Prolonged suction of membrane also influences open–closed fluctuations—it decreases channel’s activity at membrane hyperpolarization and, in contrary, increases channel’s activity at high voltages. Both membrane strain and its “fatigue” reduce dynamical complexity of channel gating, which suggest decrease in the number of available open conformations of channel protein in stressed membranes.

The large-conductance voltage- and Ca${}^{2+}$-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.