Thermo-TRP Channels: Biophysics of Polymodal Receptors

Abstract

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.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…As opposed to voltage-gated channels that only sense changes in the transmembrane electrical field, TRP channels are polymodal (i.e., integrators of various cellular signals), a property that renders them coincidence detectors (Ramsey et al, 2006;Nieto-Posadas et al, 2011). The role of TRP channels in temperature sensing is well established TRP Channels as Drug Targets (Baez-Nieto et al, 2011). However, the list of thermoTRPs is expected to shrink/change in the near future because a number of postulated temperature-sensitive TRP channels (including TRPV2, TRPV3, TRPM4, and TRPM5) are probably not functionally involved in thermosensing.…”

“…However, the list of thermoTRPs is expected to shrink/change in the near future because a number of postulated temperature-sensitive TRP channels (including TRPV2, TRPV3, TRPM4, and TRPM5) are probably not functionally involved in thermosensing. The mechanisms by which TRP channels detect changes in temperature are not clear (for critical reviews, see Latorre, 2009;Baez-Nieto et al, 2011;Voets, 2012;Jara-Oseguera and Islas, 2013).…”

The Chimeric Approach Reveals That Differences in the TRPV1 Pore Domain Determine Species-specific Sensitivity to Block of Heat Activation

“…The superfamily of transient receptor potential (TRP) 3 cation channels plays a major role in sensory transduction including vision, touch, hearing, thermosensation, taste sensation, osmosensation, and pain sensation (1)(2)(3)(4)(5)(6)(7)(8).…”

Positive selection acted on the extracellular transmembrane linkers of heat receptors during evolution

“…It is likely that the transmembrane domain may work to discriminate different types of stimulation, such as mechanical and chemical, while the loop region may be involved in heat/cold sensing. Several studies have suggested that the extracellular loop might be the primary domain for the thermal senses (Baez-Nieto et al, 2011). Grandl et al (2010 found that three residues are fundamental for temperature activation, and these residues (Ile644, Asn647 and Tyr661) are also all located in the extracellular loop between the P-loop and TM6.…”