Spatiotemporal relationships defining the adaptive gating of the bacterial mechanosensitive channel MscS.

Adaptive desensitization and inactivation are common properties of most ion channels and receptors. The mechanosensitive channel of small conductance MscS, which serves as a low-threshold osmolyte release valve in most bacteria, inactivates not from the open, but from the resting state under moderate tensions. This mechanism enables the channel to respond differently to slow tension ramps versus abruptly applied stimuli. In this work, we present a reconstruction of the energy landscape for MscS transitions based on patch current kinetics recorded under special pressure protocols. The data are analyzed with a three-state continuous time Markov model, where the tension-dependent transition rates are governed by Arrhenius-type relations. The analysis provides assignments to the intrinsic opening, closing, inactivation, and recovery rates as well as their tension dependencies. These parameters, which define the spatial (areal) distances between the energy wells and the positions of barriers, describe the tension-dependent distribution of the channel population between the three states and predict the experimentally observed dynamic pulse and ramp responses. Our solution also provides an analytic expression for the area of the inactivated state in terms of two experimentally accessible parameters: the tension at which inactivation probability is maximized, γ*, and the midpoint tension for activation, γ