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

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.