Quantifying and Modeling the Temperature-Dependent Gating of TRP Channels

The ability to sense environmental temperatures and to avoid noxious heat or cold is crucial for the survival of all organisms. In mammals, sensory neurons from dorsal root and trigeminal ganglia convey thermal information from the skin, mouth and nose to the central nervous system. Recent evidence has established that thermoTRPs, a subset of the TRP superfamily of cation channels, act as primary temperature sensors in cold- and heat-sensitive neurons. The gating of these thermoTRPs exhibits strong temperature dependence, leading to steep changes in inward current upon heating or cooling. The origin of this striking temperature sensitivity remains incompletely understood. In this review, I propose criteria that define a thermoTRP, analyse the usefulness and limitations of the commonly used parameters thermal threshold and Q(10), provide an overview of possible thermodynamic principles and gating schemes for thermosensitive TRP channels, and perform a meta-analysis of published work on the molecular basis of the heat sensitivity in TRPV1. This review may form a useful reference for the analysis and interpretation of further biophysical and structure-function studies dissecting the molecular basis of thermosensitivity in TRP channels.