The Role of TRP Channels in Thermosensation

Excerpt

We feel a wide range of temperatures spanning from coldness to heat. Within this range, temperatures over about 43°C and below about 15°C evoke not only a thermal sensation, but also a feeling of pain (LaMotte and Campbell, 1978; Tillman et al., 1995). Neurophysiological studies have demonstrated that the heat threshold of so-called C-fiber mechanoheat nociceptors (CMHs) depends on the absolute temperature, rather than the rate of temperature increase, and that the transduction of heat stimuli occurs at different skin depths for different CMHs (Tillman et al., 1995). Extreme cold also activates a subset of nociceptive neurons. However, the physiology of cold-evoked pain is not as well understood as that of heat-evoked pain. It has been hypothesized that cutaneous nociceptor endings detect temperature and other physical stimuli by means of ion channels responsive to these stimuli. The first support for this hypothesis came from the identification of heat-gated ion channels present in a subset of primary afferent neurons (Cesare and McNaughton, 1996; Reichling and Levine, 1997). Insight into the molecular nature of these channels came shortly thereafter, with the cloning of the capsaicin receptor, TRPV1 (also known as VR1, the first member of the TRPV subfamily) and the recognition that this ion channel protein, like mammalian nociceptors, could be activated by elevated temperatures with a discrete threshold near 43°C (Caterina et al., 1997; Caterina and Julius, 2001). Three other TRPV channels—TRPV2 (also known as VRL-1), TRPV3, and TRPV4 (also known as VROAC or OTRPC4)—have been cloned and characterized as heat or warm thermosensors (Jordt et al., 2003; Patapoutian et al., 2003; Tominaga and Caterina, 2004). In addition, two TRPM channels (TRPM4 and TRPM5) have been recently reported to be thermosensitive (Talavera et al., 2005). The threshold temperatures for activation of these channels range from relatively warm (TRPV3, TRPV4, TRPM4, and TRPM5) to extremely hot (TRPV2). In contrast to these warmth- or heat-activated TRP channels, two other TRP channels—TRPM8 (also known as CMR1) and TRPA1 (also known as ANKTM1)—are activated by cold stimuli (Jordt et al., 2003; Patapoutian et al., 2003; Tominaga and Caterina, 2004). This chapter focuses on eight mammalian thermosensitive TRP channels (Figure 20.1).