Ion-channel mechanisms revealed

Magleby, Karl L.

doi:10.1038/nature21103

Cited by 10 publications

(11 citation statements)

References 11 publications

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“… 25 − 27 It allowed not only for the inference that voltage and Ca 2+ sensors are coupled and they can cooperatively influence the channel pore gate domain, but also these studies failed to identify a physical gate that could mechanically block the ion flow in the nonconducting state. 28 From this point of view, the pore-forming helices do not form a tight bundle as in some Shaker-like channels to dam K + transport through the pore. In ref ( 25 ), the authors observed four different structures for the BK channel when the channel was neither voltage-activated nor Ca 2+ -activated.…”

Section: Introductionmentioning

confidence: 99%

“…It can be assumed that Hite et al 25 , 29 have identified some of the structures corresponding to different kinetic states, providing insight into which conformational states’ functionally closed and open states might be adopted. 28 Still, some questions arise, among others: Where is the actual channel gate that allows for conducting/nonconducting fluctuations at fixed conditions? What kind of and how many stable structures of the BK channel protein exist at intermediate Ca 2+ and/or voltage levels?…”

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: 99%

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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“…The branching logical function (10) that emerges is enabled by particular proteins: namely voltage gated ion channels imbedded in axon and dendrite membranes (Catterall, 2000; Randall et al, 2002; Magleby, 2017, p. 146–151) (see Figures 3, 4). They control the flow of potassium, sodium, and chloride ions, leading to action potential spike chain propagation along the axons and dendrites.…”

Section: Linking Physics and Biology: The Physical Basismentioning

confidence: 99%

“…In summary, Given the right cellular context (Hofmeyr, 2017), biomolecules such as ion channels (Catterall, 2000; Magleby, 2017) can act as logic gates, underlying the emergence of complex life processes where branching logic occurs at the higher levels of physiological systems (Rhoades and Pflanzer, 1989; Campbell and Reece, 2005; Goelzer et al, 2008; Kandel et al, 2013).…”

Section: Linking Physics and Biology: The Physical Basismentioning

confidence: 99%

The Dynamical Emergence of Biology From Physics: Branching Causation via Biomolecules

Ellis

Kopel

2019

Front. Physiol.

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Biology differs fundamentally from the physics that underlies it. This paper1 proposes that the essential difference is that while physics at its fundamental level is Hamiltonian, in biology, once life has come into existence, causation of a contextual branching nature occurs at every level of the hierarchy of emergence at each time. The key feature allowing this to happen is the way biomolecules such as voltage-gated ion channels can act to enable branching logic to arise from the underlying physics, despite that physics per se being of a deterministic nature. Much randomness occurs at the molecular level, which enables higher level functions to select lower level outcomes according to higher level needs. Intelligent causation occurs when organisms engage in deduction, enabling prediction and planning. This is possible because ion channels enable action potentials to propagate in axons. The further key feature is that such branching biological behavior acts down to cause the underlying physical interactions to also exhibit a contextual branching behavior.

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“…The logical structure of what happens is enabled by particular proteins: namely voltage gated ion channels in axon and dendrite membranes ( [25,71], [98]:146-151) (see Figs 3 and 4). They lead to controlled flow of sodium, potassium and chloride ions into and out of the axons and dendrites, leading to action potential spike chain propagation along the axons and dendrites.…”

Section: The Link Of Physics To Logic: the Molecular Basismentioning

confidence: 99%

On the Difference between Physics and Biology: Logical Branching and Biomolecules

Ellis¹,

Kopel²

2017

Preprint

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Physical emergence -crystals, rocks, sandpiles, turbulent eddies, planets, starsis fundamentally different from biological emergence -amoeba, cells, mice, humanseven though the latter is based in the former. This paper 1 points out that an essential difference is that as well as involving physical causation, causation in biological systems has a logical nature at each level of the hierarchy of emergence, from the biomolecular level up. The key link between physics and life enabling this to happen is provided by biomolecules, such as voltage gated ion channels, which enable branching logic to emerge from the underlying physics and hence enable logically based cell processes to take place in general, and in neurons in particular. These molecules can only have come into being via the contextually dependent processes of natural selection, which selects them for their biological function. A further major difference is between life in general and intelligent life. We characterise intelligent organisms as being engaged in deductive causation, which enables them to transcend the physical limitations of their bodies through the power of abstract thought, prediction, and planning. Ultimately this is enabled by the biomolecules that underlie the propagation of action potentials in neuronal axons in the brain.1 This paper is based in an FQXI essay written by one of us (GE), and is a companion to a paper with Philippe Binder on the relation between computation and physical laws [14].

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Ion-channel mechanisms revealed

Cited by 10 publications

References 11 publications

Multifractal Properties of BK Channel Currents in Human Glioblastoma Cells

Multifractal Properties of BK Channel Currents in Human Glioblastoma Cells

The Dynamical Emergence of Biology From Physics: Branching Causation via Biomolecules

On the Difference between Physics and Biology: Logical Branching and Biomolecules

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