Sensing hot and cold with TRP channels

The past decade has witnessed the cloning of a new family of ion channels that are responsive to temperature. Six of these transient receptor potential (TRP) channels are proposed to be involved in thermosensation and are located in sensory nerves and skin. The TRPV1, TRPV2, TRPV3, and TRPV4 channels have incompletely overlapping functions over a broad thermal range from warm to hot. Deletion of the individual TRPV1, TRPV3, and TRPV4 channels in mice has established their physiological role in thermosensation. In all cases thermosensation is not completely abolished -- suggesting some functional redundancy among the channels. Notably, the TRPV2 channel is responsive to hot temperatures in heterologous systems, but its physiological relevance in vivo has not been established. Cool and cold temperatures are sensed by TRPM8 and TRPA1 family members. Currently, the pharmaceutical industry is developing agonists and antagonists for the various TRP channels. For instance, TRPV1 receptor agonists produce hypothermia, while antagonists induce hyperthermia. Recent investigations have found that different regions of the TRPV1 receptor are responsive to temperature, nociceptive stimuli, and various chemical agents. With this information, it has been possible to develop a TRPV1 compound that blocks responses to capsaicin and acid while leaving temperature sensitivity intact. These channels have important implications for hyperthermia research and may help to identify previously unexplored mechanisms in different tissues that are responsive to thermal stress.