M De la Fuente I et al. (2017), Dynamic properties of calcium-activated chlorid...

XB-ART-53115

Sci Rep 2017 Feb 13;7:41791. doi: 10.1038/srep41791.

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Dynamic properties of calcium-activated chloride currents in Xenopus laevis oocytes.

M De la Fuente I, Malaina I, Pérez-Samartín A, Boyano MD, Pérez-Yarza G, Bringas C, Villarroel Á, Fedetz M, Arellano R, Cortes JM, Martínez L.

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Chloride is the most abundant permeable anion in the cell, and numerous studies in the last two decades highlight the great importance and broad physiological role of chloride currents mediated anion transport. They participate in a multiplicity of key processes, as for instance, the regulation of electrical excitability, apoptosis, cell cycle, epithelial secretion and neuronal excitability. In addition, dysfunction of Cl- channels is involved in a variety of human diseases such as epilepsy, osteoporosis and different cancer types. Historically, chloride channels have been of less interest than the cation channels. In fact, there seems to be practically no quantitative studies of the dynamics of chloride currents. Here, for the first time, we have quantitatively studied experimental calcium-activated chloride fluxes belonging to Xenopus laevis oocytes, and the main results show that the experimental Cl- currents present an informational structure characterized by highly organized data sequences, long-term memory properties and inherent "crossover" dynamics in which persistent correlations arise at short time intervals, while anti-persistent behaviors become dominant in long time intervals. Our work sheds some light on the understanding of the informational properties of ion currents, a key element to elucidate the physiological functional coupling with the integrative dynamics of metabolic processes.

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Species referenced: Xenopus laevis
Genes referenced: nr4a1

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	Figure 1. Calcium-activated chloride currents in Xenopus laevis oocyte.Three prototype experimental Cl− currents obtained from the same cell at different conditions: (a) pH 5.0 (n10), (b) pH 7.0 (n11), (c) pH 9.0 (n12). Each chloride time series has 130,000 points (sampling interval 2 milliseconds), which correspond to a period of time of 260,000 milliseconds duration. The vertical axis (Φ) corresponds to the measures of currents in nanoampers (nA).
	Figure 2. Ca2+-dependent Cl− current validation.(a) Xenopus oocyte held at either −60, −40, −20 or 0 mV. Reversal potential of oscillatory currents corresponded to a value close to −23 mV. (b) Oscillatory current reversal potential were dependent on external Cl− concentration, traces show currents in oocytes held at −30 mV or 0 mV in 3 different solutions containing 100%, 50% or 0% Cl−, reversal potential shifted toward more positive potentials as external Cl− concentration decreased. (c) Cytoplasmic injection of EGTA, a Ca2+ chelator, completely eliminated the oscillatory Cl− current.
	Figure 3. Root mean square fluctuation analysis applied to experiment 1 on a single window.Log-log plot of the rms fluctuation F versus l step. The red points depict the results of the original data for each value of l, while the black lines represent the regression lines. (a) α = 0.88 (n1), (b) α = 0.92 (n2) and (c) α = 0.83 (n3). Corresponding (respectively) R2 adjustment coefficients were 0.9915, 0.9921 and 0.9976. The high values of α and R2 indicate non-trivial long-term correlations for each chloride time series during 10, 13 and 12 seconds respectively.
	Figure 4. Long-term correlations across different windows lengths.(a) Global average versus different values of lmax (varying from 1 to 24 seconds). (b) as a function of lmax (varying from 25 to 40 seconds). The error bars represent the standard deviation at each step. It can be observed that all Cl− time series change from positive to negative correlation near lmax = 28 seconds.
	Figure 5. Hurst exponents obtained by the bdSWV analysis.(a) The slope of a log-log plot of the versus the window size for a bdWSV applied to an evoked chloride series (n13, experiment 5, pH = 5.0) gives H = 0.104, indicating the presence of long-term memory. (b) The slope of a log-log plot of the SD(n) versus the window size for a Dispersion Analysis applied to shuffled time series obtained by randomly permuting all the 130,000 time points for each Cl− time series (n13). After shuffling, H was close to 0.5, indicating the disappearance of the memory structure. (c) In red, Hurst exponent values of all the experimental chloride time series; in blue, 100 Hurst exponent values obtained from shuffled series.

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