In this chapter we discuss the polymodal activation of thermo-TRP channels using as exemplars two of the best characterized members of this class of channels: TRPM8 and TRPV1. Since channel activation by temperature is the hallmark of thermo-TRP channels, we present a detailed discussion on the thermodynamics involved in the gating processes by temperature, voltage, and agonists. We also review recently published data in an effort to put together all the pieces available of the amazing puzzle of thermo-TRP channel activation. Special emphasis is made in the structural components that allow the channel-forming proteins to integrate such diverse stimuli, and in the coupling between the different sensors and the ion conduction pathway. We conclude that the present data is most economically explained by allosteric models in which temperature, voltage, and agonists act separately to modulate channel activity.
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Thermo-TRP regulation by endogenous factors and its physiological function at core body temperature.
Physiol Rep
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Transient receptor potential (TRP) channels with temperature sensitivities (thermo-TRPs) are involved in various physiological processes. Thermo-TRPs that detect temperature changes in peripheral sensory neurons possess indispensable functions in thermosensation, eliciting defensive behavior against noxious temperatures and driving autonomic/behavioral thermoregulatory responses to maintain body temperature in mammals. Moreover, most thermo-TRPs are functionally expressed in cells and tissues where the temperature is maintained at a constant core body temperature.
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J Physiol Sci
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Article Synopsis
- Body temperature plays a crucial role in animal activities and health, with even a slight increase (0.5 °C) potentially causing headaches in humans.
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TRPV Ion channels are sophisticated molecular sensors designed to respond to distinct temperature thresholds. The recent surge in cryo-EM structures has provided numerous insights into the structural rearrangements accompanying their opening and closing; however, the molecular mechanisms by which TRPV channels establish precise and robust temperature sensing remain elusive. In this work we employ molecular simulations, multi-ensemble contact analysis, graph theory, and machine learning techniques to reveal the temperature-sensitive residue-residue interactions driving allostery in TRPV3.
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Cold thermoreceptor neurons detect temperature drops with highly sensitive molecular machinery concentrated in their peripheral free nerve endings. The main molecular entity responsible for cold transduction in these neurons is the thermo-TRP channel TRPM8. Cold, cooling compounds such as menthol, voltage, and osmolality rises activate this polymodal ion channel.
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