Biophysical and molecular features of thermosensitive TRP channels involved in sensory transduction

Abstract

Temperature is one of the physical variables that cells and biological organisms constantly monitor to achieve homeostasis and maintain chemical reactions at a suitable speed for the living environment to which they are adapted. In order to monitor and maintain temperature on a constant basis, thermosensitive molecules were selected during evolution. One of the most remarkable sets of molecules acting as sensors is constituted by thermosensitive transient receptor potential channels (thermoTRP channels). TRP channels are a superfamily of non-selective tetrameric cation channels closely related to the classic superfamily of voltagegated channels, having a set of distinctive sequence elements in common, while acting as polymodal receptors. This latter ability is what makes them suitable for integrating many kinds of signals in different cells, ranging from chemical to physical stimulation ( i.e.: temperature-, mechano- and chemo-sensitivity). These channels act as allosteric proteins modifying sensitivity to one stimulus in the presence of another, and thus allowing the integration of many different signaling processes that are critical for sensing the extracellular and intracellular environment and for maintaining homeostasis. This ability has made them vital for life support. Several subfamilies of TRP channels have been described. From these subfamilies, some types of channels have been distinguished as being temperature-sensitive, such as TRPV1-4, TRPM 2-5/8, TRPA1 and TRPC5. In this chapter, thermosensitivity will be defined. Then, we will describe the thermosensitive molecules identified so far, focusing our analysis on ion channels, particularly on thermosensitive TRP channels involved in sensory transduction. Their gating and permeation properties and gating modifiers shall be at the center of the discussion so as to place them in the context of ion channels and life evolution.