Demystifying Thermal Channels: Driving a Channel both Forwards and Backwards with a Single Gear?

Feng, Qicheng

doi:10.1016/j.bpj.2013.04.017

Cited by 12 publications

(9 citation statements)

References 11 publications

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“…However, how thermal TRP channels achieve their unique biophysical properties remains elusive. One outstanding issue has been how temperature is sensed by the channels (13). As a nonspecific stimulus, temperature can influence every part of a protein.…”

Section: Introductionmentioning

confidence: 99%

Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2

Liu

Feng

2016

Biophysical Journal

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Thermal TRP channels mediate temperature transduction and pain sensation. The vanilloid receptor TRPV2 is involved in detection of noxious heat in a subpopulation of high-threshold nociceptors. It also plays a critical role in development of thermal hyperalgesia, but the underlying mechanism remains uncertain. Here we analyze the heat sensitivity of the TRPV2 channel. Heat activation of the channel exhibits strong use dependence. Prior heat activation can profoundly alter its subsequent temperature responsiveness, causing decreases in both temperature activation threshold and slope sensitivity of temperature dependence while accelerating activation time courses. Notably, heat and agonist activations differ in cross use-dependence. Prior heat stimulation can dramatically sensitize agonist responses, but not conversely. Quantitative analyses indicate that the use dependence in heat sensitivity is pertinent to the process of temperature sensing by the channel. The use dependence of TRPV2 reveals that the channel can have a dynamic temperature sensitivity. The temperature sensing structures within the channel have multiple conformations and the temperature activation pathway is separate from the agonist activation pathway. Physiologically, the use dependence of TRPV2 confers nociceptors with a hypersensitivity to heat and thus provides a mechanism for peripheral thermal hyperalgesia.

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Section: Introductionmentioning

confidence: 99%

Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2

Liu

Feng

2016

Biophysical Journal

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“…The allosteric linkage can have a temperature dependence to either promote or inhibit channel opening, thereby making the channel sensitive to the direction of temperature changes. Presently, these models still lack direct experimental support ( Qin, 2013 ). The study of the opposite temperature sensitivity of homologous thermal channels could provide an opportunity to experimentally elucidate these models and the principles of temperature gating of thermal channels in general.…”

Section: Introductionmentioning

confidence: 99%

The Xenopus tropicalis orthologue of TRPV3 is heat sensitive

Liu

Feng

2015

Journal of General Physiology

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Thermosensitive members of the transient receptor potential (TRP) family of ion channels (thermal TRP channels) play a crucial role in mammalian temperature sensing. Orthologues of these channels are present in lower vertebrates and, remarkably, some thermal TRP orthologues from different species appear to mediate opposing responses to temperature. For example, whereas the mammalian TRPV3 channel is activated by heat, frog TRPV3 is reportedly activated by cold. Intrigued by the potential implications of these opposing responses to temperature for the mechanism of temperature-dependent gating, we cloned Xenopus laevis TRPV3 and functionally expressed it in both mammalian cell lines and Xenopus oocytes. We found that, when expressed in mammalian cells, the recombinant channel lacks the reported cold sensitivity; rather, it is activated by temperatures >50°C. Furthermore, when expressed in mammalian cells, the frog orthologue shows other features characteristic of mammalian TRPV3, including activation by the agonist 2-aminoethoxydiphenyl borate and an increased response with repeated stimulation. We detected both heat- and cold-activated currents in Xenopus oocytes expressing the recombinant frog TRPV3 channel. However, cold-activated currents were also apparent in control oocytes lacking recombinant TRPV3. Our data indicate that frog TRPV3 resembles its mammalian orthologues in terms of its thermosensitivity and is intrinsically activated by heat. Thus, all known vanilloid receptors are activated by heat. Our data also show that Xenopus oocytes contain endogenous receptors that are activated by cold, and suggest that cold sensitivity of TRP channels established using Xenopus oocytes as a functional expression system may need to be revisited.

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“…It remains unknown what is the structural and energetic basis for the large enthalpy change that dictates the high temperature sensitivity of TRPV1 gating [52]. Various models were proposed based on solvation/de-solvation of nonpolar/polar residues [53,54], or denaturation of heat-sensing domain [55]. Recently, a study by Sanchez-Moreno et al provided evidence that denaturation or a similar irreversible mechanism might participate in TRPV1 temperature gating [56].…”

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confidence: 99%

Heat activation mechanism of TRPV1: New insights from molecular dynamics simulation

Zheng

Wen

2019

Temperature

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As a member of the transient receptor potential (TRP) channels superfamily, the TRPV1 channel undergoes a closed-to-open gating transition in response to various physical and chemical stimuli including heat. Thanks to recent progress in cryo-electron microscopy, high-resolution structures are becoming available for various TRP channels including TRPV1. This has enabled us to study the molecular mechanism of TRPV1 channel gating by using molecular simulation. Here we review recent progress in molecular simulations of TRPV1 channel by us and others, with focus on our molecular dynamics (MD) simulations of TRPV1 at different temperatures. While no consensus has been reached on the heat activation mechanism of TRPV1, the simulations have offered specific predictions and models for future experimental studies to test.

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Demystifying Thermal Channels: Driving a Channel both Forwards and Backwards with a Single Gear?

Cited by 12 publications

References 11 publications

Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2

Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2

The Xenopus tropicalis orthologue of TRPV3 is heat sensitive

Heat activation mechanism of TRPV1: New insights from molecular dynamics simulation

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