Extracting thermodynamic properties from van ’t Hoff plots with emphasis on temperature-sensing ion channels

Abstract

ABSTRACTTransient receptor potential (TRP) ion channels are among the most well-studied classes of temperature-sensing molecules. Yet, the molecular mechanism and thermodynamic basis for the temperature sensitivity of TRP channels remains to this day poorly understood. One hypothesis is that the temperature-sensing mechanism can simply be described by a difference in heat capacity between the closed and open channel states. While such a two-state model may be simplistic it nonetheless has descriptive value, in the sense that it can be used to compare overall temperature sensitivity between different channels and mutants. Here, we introduce a mathematical framework based on the two-state model to reliably extract temperature-dependent thermodynamic potentials and heat capacities from measurements of equilibrium constants at different temperatures. Our framework is implemented in an open-source data analysis package that provides a straightforward way to fit both linear and nonlinear van ’t Hoff plots, thus avoiding some of the previous, potentially erroneous, assumptions when extracting thermodynamic variables from TRP channel electrophysiology data.KEYWORDS: TRP channelstemperature sensorsvan ’t Hoff plotsthermodynamicsspline fitting AcknowledgmentsWe thank Dr. Andrés Jara-Oseguera for fruitful discussions and critical comments on the manuscript. The Flatiron Institute is a division of the Simons Foundation.Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThis work was supported by the Max-Planck-Gesellschaft (JTB) and the Simons Foundation (SMH).