Mechanosensitivity of the BK Channels in Human Glioblastoma Cells: Kinetics and Dynamical Complexity

Wawrzkiewicz-Jałowiecka, Agata; Trybek, Paulina; Machura, Łukasz; Dworakowska, Beata; Grzywna, Zbigniew J.

doi:10.1007/s00232-018-0044-9

Cited by 13 publications

(9 citation statements)

References 48 publications

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“…Second, gBK channels are anticipated to provide the electrochemical driving force for the ion movement needed for the release of cytoplasmic water and cell shrinkage, which in turn facilitates the extensive migrating behavior of glioblastoma cells. This was indicated by the results provided in the works of Wondergem et al , Moreover, due to the mechanosensitivity of gBK channels, they may be involved in the mechanotransduction during cell shape and volume changes . Also deformation or reorganization of the cytoskeleton during an alteration in cell volume or shape may affect the functioning of gBK channels, which, as a consequence, should affect the effectiveness of cell migration.…”

Section: Introductionmentioning

confidence: 89%

“…This was indicated by the results provided in the works of Wondergem et al 15 , 16 Moreover, due to the mechanosensitivity of gBK channels, they may be involved in the mechanotransduction during cell shape and volume changes. 17 Also deformation or reorganization of the cytoskeleton during an alteration in cell volume or shape may affect the functioning of gBK channels, 17 which, as a consequence, should affect the effectiveness of cell migration.…”

Section: Introductionmentioning

confidence: 99%

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Multifractal Properties of BK Channel Currents in Human Glioblastoma Cells

Wawrzkiewicz-Jałowiecka

Trybek

Dworakowska

et al. 2020

J. Phys. Chem. B

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Potassium channels play an important physiological role in glioma cells. In particular, voltage- and Ca 2+ -activated large-conductance BK channels (gBK in gliomas) are involved in the intensive growth and extensive migrating behavior of the mentioned tumor cells; thus, they may be considered as a drug target for the 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 relate to its functional properties (conducting/nonconducting). 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 nonconducting (functionally closed) and conducting (open) states. The details of channel conformational diffusion ought to have its representation in the properties of the experimental signal that describes the ion-channel activity. Nonlinear methods of analysis of experimental nonstationary series can be useful for observing the changes in the number of channel substates available from geometrical and energetic points of view at given external conditions. In this work, we analyze whether the multifractal properties of the activity of glioblastoma BK channels depend on membrane potential, and which states, conducting or nonconducting, affect the total signal to a larger extent. With 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 using 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 the analysis of an experimental patch-clamp time series. The obtained results suggest that membrane potential strongly affects the conformational space of the gBK channel proteins and the considered process has nonlinear multifractal characteristics. These properties are the inherent features of the analyzed signals due to the fact that the main tendencies vanish after shuffling the data.

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Multifractal Properties of BK Channel Currents in Human Glioblastoma Cells

Wawrzkiewicz-Jałowiecka

Trybek

Dworakowska

et al. 2020

J. Phys. Chem. B

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“…(3) Glioblastoma invasiveness in the brain parenchyma: When a GBM cell invades the extracellular matrix in the brain, the process requires a reduction of cytosolic volume. The increase in pressure that the extracellular matrix exerts on the GBM cell induces mechanical stress on the membrane, which has been suggested to activate BK channels (Zhao et al, 2010;Wawrzkiewicz-Jałowiecka et al, 2018). Moreover, this mechanical constraint might lead to a possible biochemical cascade with a consequent increase of intracellular calcium concentration that shifts the voltage activation curve of the channel to a more hyperpolarized potential (Charles et al, 1991).…”

Section: Kir41 and Bk Channels: A Summative Link?mentioning

confidence: 99%

Deeper and Deeper on the Role of BK and Kir4.1 Channels in Glioblastoma Invasiveness: A Novel Summative Mechanism?

et al. 2020

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In the last decades, increasing evidence has revealed that a large number of channel protein and ion pumps exhibit impaired expression in cancers. This dysregulation is responsible for high proliferative rates as well as migration and invasiveness, reflected in the recently coined term oncochannelopathies. In glioblastoma (GBM), the most invasive and aggressive primary brain tumor, GBM cells modify their ionic equilibrium in order to change their volume as a necessary step prior to migration. This mechanism involves increased expression of BK channels and downregulation of the normally widespread Kir4.1 channels, as noted in GBM biopsies from patients. Despite a large body of work implicating BK channels in migration in response to an artificial intracellular calcium rise, little is known about how this channel acts in GBM cells at resting membrane potential (RMP), as compared to other channels that are constitutively open, such as Kir4.1. In this review we propose that a residual fraction of functionally active Kir4.1 channels mediates a small, but continuous, efflux of potassium at the more depolarized RMP of GBM cells. In addition, coinciding with transient membrane deformation and the intracellular rise in calcium concentration, brief activity of BK channels can induce massive and rapid cytosolic water loss that reduces cell volume (cell shrinkage), a necessary step for migration within the brain parenchyma.

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“…Additionally, TREK-2-like channels and K BK channels have distinct kinetics. K BK channels are strongly voltage-dependent, and even at high calcium concentrations, a large difference in activity between the hyperpolarized and depolarized potentials is present [ 68 ]. TREK-2-like channels are weakly voltage-dependent, and their activity at hyperpolarized potentials is often of similar intensity as at depolarized potentials ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

Activity of TREK-2-like Channels in the Pyramidal Neurons of Rat Medial Prefrontal Cortex Depends on Cytoplasmic Calcium

Dworakowska

Gawlak

Nurowska

2021

Biology

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TREK-2-like channels in the pyramidal neurons of rat prefrontal cortex are characterized by a wide range of spontaneous activity—from very low to very high—independent of the membrane potential and the stimuli that are known to activate TREK-2 channels, such as temperature or membrane stretching. The aim of this study was to discover what factors are involved in high levels of TREK-2-like channel activity in these cells. Our research focused on the PI(4,5)P2-dependent mechanism of channel activity. Single-channel patch clamp recordings were performed on freshly dissociated pyramidal neurons of rat prefrontal cortexes in both the cell-attached and inside-out configurations. To evaluate the role of endogenous stimulants, the activity of the channels was recorded in the presence of a PI(4,5)P2 analogue (PI(4,5)P2DiC8) and Ca2+. Our research revealed that calcium ions are an important factor affecting TREK-2-like channel activity and kinetics. The observation that calcium participates in the activation of TREK-2-like channels is a new finding. We showed that PI(4,5)P2-dependent TREK-2 activity occurs when the conditions for PI(4,5)P2/Ca2+ nanocluster formation are met. We present a possible model explaining the mechanism of calcium action.

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Mechanosensitivity of the BK Channels in Human Glioblastoma Cells: Kinetics and Dynamical Complexity

Cited by 13 publications

References 48 publications

Multifractal Properties of BK Channel Currents in Human Glioblastoma Cells

Multifractal Properties of BK Channel Currents in Human Glioblastoma Cells

Deeper and Deeper on the Role of BK and Kir4.1 Channels in Glioblastoma Invasiveness: A Novel Summative Mechanism?

Activity of TREK-2-like Channels in the Pyramidal Neurons of Rat Medial Prefrontal Cortex Depends on Cytoplasmic Calcium

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