Thermoregulation without the set point: roles of TRP Channels

      The thermoregulation system is a federation of relatively independent thermoeffector loops coordinated by the overlapping control variables (“body temperatures, Tb’s”). Each thermoeffector response is driven by a unique combination of Tb’s. Some superficial (of hairy skin) and deep (of hypothalamus) Tb’s are considered most important. Tb signals from the skin are converted into electric signals by temperature-sensitive transient receptor potential (TRP) channels, and possibly other “thermosensors.” This symposium will review the roles of different TRP channels in thermoregulation. Skin Tb signals that drive thermoeffectors responses for defense against cold, at least most of these responses and at least in rodents, are generated by TRPM8 (and possibly other channels), but not TRPA1. We did not quantify contributions of skin Tb’s vs. brain Tb’s to cold defenses, but our experiments show clearly that skin signals are physiologically important. Skin Tb signals that drive warmth-defense thermoeffector responses in rodents are generated by TRPV3 and TRPV4 (and possibly other channels), but not TRPV1. However, our experiments show that the role of skin Tb’s in driving these responses is usually unimportant. Skin TRPV1 does not seem to be involved in converting skin Tb signals into electric signals driving thermoeffectors. However, visceral TRPV1 channels are tonically activated by protons, and these low-pH signals suppress at least some cold-defense responses in several mammal species, including humans and rodents.
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