Dynamics of the membrane potential : Studies of the membrane potential of Jurkat cells using wavelet and wavelet bispectral analysis

Pidde, Aleksandra and Stefanovska, Aneta and Montbrió, Ernest (2020) Dynamics of the membrane potential : Studies of the membrane potential of Jurkat cells using wavelet and wavelet bispectral analysis. PhD thesis, Lancaster University.

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Abstract

Fluctuations are fundamental for living organisms. They arguably result from interactions with the complex, and unpredictable environment, and can often be manifested as temporal variability. Let us consider the smallest representative of living organisms, the cell. It must continually resist the external perturbations, such as variations in the electrochemical gradient induced by changes in the extracellular ionic concentrations. To avoid the rise in osmotic pressure, that drives the water into the cell and could result in the cell bursting, the cell carefully adjusts the concentration of permeable ions. Those continuous adjustments can be achieved only through a highly specialised network of membrane transporters, both passive, ion channels, and active, ion pumps. The collective activity of the membrane transporters is manifested in the dynamics of the membrane potential -- very often viewed as fluctuations, seemingly without a preference for any particular frequency band. The aim of the work presented here is to provide understanding and insight into the dynamics of the free-running membrane potential in non-excitable cells, based on experimental data from Jurkat and smooth muscle cells. In order to achieve this, first the quantitative comparisons of the average values of the membrane potential and their standard deviations recorded in various extracellular solutions are made. The analysis is further extended through the use of the wavelet transform to investigate the time and frequency components of the signal. This work is the first to report an intermittent oscillation in smooth muscle cell, around 0.008 Hz in the membrane potential recorded with the free-running voltage perforated whole-cell patch clamp method. Additional activities around frequencies of 0.03, 0.05 or 0.09 Hz can be also observed. These appear as intermittent behaviour. To further understand this dynamics from univariate time series, two methods were applied: wavelet-bispectrum and time-reversibility. The wavelet-bispectral density was developed. An appropriate normalisation for the wavelet bispectrum, that allows for a formal quantitative, not merely qualitative interpretation of the results of wavelet-bispectral analysis, was proposed. The practical aspects of the bispectral analysis were discussed using numerical examples. Finally, the newly developed auto-wavelet-bispectral analysis was applied to the recordings of the membrane potential. These indicated possible nonlinear couplings between different oscillatory modes in the cellular membrane potential.