Dynamical diversity of mitochondrial BK channels located in different cell types

Abstract

Mitochondrial large-conductance voltage- and Ca²⁺-activated potassium channels (mitoBK) exhibit substantial similarities in their physiology regardless of the channel's location. Nevertheless, depending on the cell type, composition of membranes can vary, and mitoBK channels can be expressed in different splice variants as well as they can be co-assembled with different types of auxiliary β subunits. These factors can modulate their voltage- and Ca²⁺-sensitivity, and single-channel current kinetics. It is still an open question to what extent the mentioned factors can affect the complexity of the conformational dynamics of the mitoBK channel gating. In this work the dynamical diversity of mitoBK channels from different cell types was unraveled by the use of nonlinear methods of analysis: multifractal detrended fluctuation analysis (MFDFA) and multiscale entropy (MSE). These techniques were applied to the experimental series of single channel currents. It turns out that the differences in the mitoBK expression systems influence gating machinery by changing the scheme of switching between the stable channel conformations, and affecting the average number of available channel conformations (this effect is visible for mitoBK channels in glioblastoma cells). The obtained results suggest also that a pathological dynamics can be represented by signals of relatively low complexity (low MSE of the mitoBK channel gating in glioblastoma).

Keywords: Focus-based multifractal analysis MFDFA; Gating dynamics; Hurst exponent by DFA method; MitoBK channels; Multiscale entropy MSE; βsubunits.