Information Entropy Metrics to Address the Complexity of Cooperative Gating of Ion Channels

Ion channels in biological membranes can form spatially localized clusters that exhibit cooperative gating behavior. In this mode, the activity of one channel modulates the opening probability of its neighbors. Understanding such inter-channel interactions is key to elucidating the molecular mechanisms underlying electrochemical signaling and advancing channel-targeted pharmacology. In this study, we introduce a simplified stochastic model of multi-channel gating that allows for systematic analysis of cooperative behavior under controlled conditions. Two information-theoretic metrics, i.e., Shannon entropy and Sample Entropy, are applied to simulated multi-channel datasets, including idealized total current traces and dwell-time sequences of cluster states, to quantify inter-channel cooperativity. We show that the entropic measures display a strong dependency on the strength and type of cooperation (non-, positive, or negative cooperation). The proposed entropy-based framework offers a generalizable and quantitative approach for biomedical data analysis, demonstrating effectiveness in interpreting multi-channel recordings and uncovering cooperative mechanisms in ion channel behavior. The underlying mechanisms by which entropy reflects cooperativity are expected to appear in real recordings, where deviations can further aid in characterizing individual channel features in future work.