Applying Entropic Measures, Spectral Analysis, and EMD to Quantify Ion Channel Recordings: New Insights into Quercetin and Calcium Activation of BK Channels

Understanding the functional modulation of ion channels by multiple activating substances is critical to grasping stimulus-specific gating mechanisms and possible synergistic or competitive interactions. This study investigates the activation of large-conductance, voltage- and Ca²⁺-activated potassium channels (BK) in the plasma membrane of human bronchial epithelial cells by Ca²⁺ and quercetin (Que), both individually and in combination. Patch-clamp recordings were analyzed using open state probability, dwell-time distributions, Shannon entropy, sample entropy, power spectral density (PSD), and empirical mode decomposition (EMD). Our results reveal concentration-dependent alterations in gating kinetics, particularly at a low concentration of quercetin ([Que] = 10 μM) compared with [Que] = 100 μM, where some Que-related effects are strongly attenuated in the presence of Ca²⁺. We also identify specific frequency bands where oscillatory components are most sensitive to the considered stimuli. Our findings highlight the complex reciprocal interplay between Ca²⁺ and Que in modulating BK channel function, and demonstrate the interpretative power of entropic and signal-decomposition approaches in characterizing stimulus-specific gating dynamics.