Direct analytical estimation of thermodynamic parameters of thermo-TRP channels

A subset of Transient Receptor Potential (TRP) channels display very steep temperature dependences and play key roles in thermosensation. To characterize the properties of these ‘thermoTRP’ channels, two-state close-open gating models were developed for TRPM8, TRPV1, TRPM4, TRPM5, TRPA1 and TRPM3. In this study, we met the recurrent challenge of finding an initial set of model parameters enabling effective convergence during data fitting procedures. We performed algebraic calculations to derive equations for all gating model parameters as functions of key features of thermoTRP channel data obtained from patch-clamp experiments. We used a minimal set of experimental data: the steady-state open probability and time constant of current relaxation as functions of the membrane potential determined at two temperatures. Specifically, we could express the electric distance of the gating charge and the enthalpy and entropy changes associated with the gating transitions, as functions of the voltages for half-maximal activation, the voltages for maximal time constant of current relaxation and the maximal time constant. Our results provide a method to analytically estimate an initial set thermoTRP thermodynamic parameters enabling robust subsequent nonlinear global data fitting. This approach facilitates quantitative analysis of channel thermodynamics, and has potential applications to more complex gating models, and to the study of permeation, block and other ion channel gating mechanisms.