New Diagnostic Tool for Ion Channel Activity Hidden Behind the Dwell-Time Correlations

[Image: see text] The patch-clamp technique is a powerful tool that allows for a long observation of transport protein activity in real time. Experimental traces of single-channel currents can be considered as a record of the channel’s conformational switching related to its activation and gating. In this work, we present a mathematically simple method of patch-clamp data analysis that assesses the connectivity and occupancy of distinct conformational substates of the channel. The proposed approach appears to be a big step forward due to its possible applications in the determination of channel substates related to disease and in the analysis of drug–channel interactions on the level of repetitive sequences of channel conformations. This is especially important in cases when molecular dynamics docking is impossible and Markovian modeling requires ambiguous optimization tasks.