Warmth-sensitive channels in thermoregulation: TRPV3 and TRPV4

      The transient receptor potencial (TRP) ion channels TRPV3 and TRPV4 are activated by innocuous warmth temperatures (34 to 39 °C and 25 to 34 °C, respectively) and are the two main candidates to function as moderate warmth receptors involved in heat defenses in mammals. Yet, their role in the recruitment of autonomic and behavioral thermoeffectors are not completely understood. A conclusive role for TRPV3 in the recruitment of autonomic thermoeffectors is still absent, although TRPV3 is important for the recruitment of behavioral effector such as grooming. Indeed, treatment with camphor (a TRPV3 agonist) increases time spent in grooming in rats and warmth-induced grooming is blocked by a TRPV3 antagonist (AMG8432). For TRPV4, substantial evidence for its involvement in the recruitment of thermoeffectors are available. In rats, chemical activation of TRPV4 by topical application of a selective agonist (RN-1747) on the skin leads to hypothermia and this effect was blocked by the pre-treatment with the selective TRPV4 antagonist. Besides, intravenous blockade of this channel with HC-067047 increases core body temperature, which, at 26 °C of ambient temperature, is accompanied by increase in oxygen consumption (index of thermogenesis), while chemical stimulation of TRPV4 increased tail heat loss, indicating that these two autonomic thermoeffectors in the rat are modulated through TRPV4 channels. Furthermore, rats chemically stimulated with TRPV4 agonist choose colder ambient temperatures and cold-seeking behaviour after thermal stimulation (28-31 °C) is inhibited by TRPV4 antagonist. These results suggest that TRPV4 channel is involved in the recruitment of behavioural and autonomic warmth-defense responses in order to regulate core body temperature. Financial Support: Fapesp and CNPq.
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