Analysis of correlations of dwell-times of adjacent kinetic states in the activity of the cold and menthol receptor TRPM8

Abstract

Temperature-sensitive transient receptor potential (TRP) channels play a significant role in intercellular signalling in response to membrane depolarisation and caclium influx. TRPM8 ion channels have been investigated as the main cold receptors (neurosensors), but they can also be activated by voltage, $Ca^{2+}$ store depletion, and certain lipids and other ligands that induce cold sensation (such as menthol and icilin). Despite recent progress in studying these channels at the single-channel level, the mechanisms and time course of their activation remain underexplored. We propose an approach to single-ion channel analysis that elucidates the presence of correlations between dwell-times of adjacent open and closed states. One of the major benefits of this approach is that it can serve as an express test of channel activity properties owing to its simplicity and fast numerical realization. The idea of our analysis is to study the difference between the distribution function derived from the given trace (simulated or experimentally recorded) and the predicted distributions of simple models without correlation. In this way, we compared the distribution function of the difference between the durations of the adjacent open and closed states of the channel, as well as that of a similar sequence of open-closed-open-closed states.