Molecular sensors and modulators of thermoreception

Abstract

The detection of temperature is one of the most fundamental sensory functions across all species, and is critical for animal survival. Animals have thus evolved a diversity of thermosensory mechanisms allowing them to sense and respond to temperature changes (thermoreception). A key process underlying thermoreception is the translation of thermal energy into electrical signals, a process mediated by thermal sensors (thermoreceptors) that are sensitive to a specific range of temperatures. In disease conditions, the temperature sensitivity of thermoreceptors is altered, leading to abnormal temperature sensation such as heat hyperalgesia. Therefore, the identification of thermal sensors and understanding their functions and regulation hold great potential for developing novel therapeutics against many medical conditions such as pain.

Keywords: TRP ion channels; pain; somatosensory transduction; temperature; thermoreception.

Figure 1.

A schematic diagram depicting the temperature sensitive ion channels. Ion channels are ordered according to their relative activation threshold to temperatures.

Figure 2.

Summary of distinct modulation of TRPV1 and TRPM8 by inflammatory mediators activating Gq coupled receptors. The inflammatory mediator BK sensitizes hyperalgesia-mediated TRPV1, but inhibits analgesia-mediated TRPM8, resulting in inflammatory hyperalgesia. The sensitization of TRPV1 is caused by the phosphorylation of TRPV1 at S502/S801 (not depicted) by PKCε, which is anchored adjacent to TRPV1 by the scaffolding protein AKAP79/150 forming a macro-signaling complex. However, the inhibition of TRPM8 is mediated by a direct action of activated Gq on TRPM8 independently of the PLC signaling. Note that the basal thermal sensitivity of TRPV1 is determined by the basal phosphorylation of TRPV1 at T705 by PKCβII, which binds to TRPV1 forming another local protein complex with TRPV1.