Differences in Gating Dynamics of BK Channels in Cellular and Mitochondrial Membranes from Human Glioblastoma Cells Unraveled by Short- and Long-Range Correlations Analysis

Abstract

The large-conductance voltage- and Ca2+-activated K+ channels (BK) are encoded in humans by the Kcnma1 gene. Nevertheless, BK channel isoforms in different locations can exhibit functional heterogeneity mainly due to the alternative splicing during the Kcnma1 gene transcription. Here, we would like to examine the existence of dynamic diversity of BK channels from the inner mitochondrial and cellular membrane from human glioblastoma (U-87 MG). Not only the standard characteristics of the spontaneous switching between the functional states of the channel is discussed, but we put a special emphasis on the presence and strength of correlations within the signal describing the single-channel activity. The considered short- and long-range memory effects are here analyzed as they can be interpreted in terms of the complexity of the switching mechanism between stable conformational states of the channel. We calculate the dependencies of mean dwell-times of (conducting/non-conducting) states on the duration of the previous state, Hurst exponents by the rescaled range R/S method and detrended fluctuation analysis (DFA), and use the multifractal extension of the DFA (MFDFA) for the series describing single-channel activity. The obtained results unraveled statistically significant diversity in gating machinery between the mitochondrial and cellular BK channels.

Keywords

• glioblastoma
• BK channels in plasma membrane
• mitochondrial BK (mitoBK) channels
• patch-clamp
• hurst exponent
• detrended fluctuation analysis (DFA)