TRPV3 and TRPV4 Ion Channels are Not Major Contributors to Mouse Heat Sensation

Huang, Susan M.; Li, Xiaoxin; Yu, Yin; Wang, Juan; Caterina, Michael J.

doi:10.1186/1744-8069-7-37

Cited by 154 publications

(163 citation statements)

References 35 publications

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“…Second, we used 129S1/SvImJ mice in these studies, and this strain may be inferior to C57BL/6 mice in behavioral assays (42,43). It has been noted that there are temperature-sensing differences between mouse strains (44,45), and we cannot generalize our results to other strains or species.…”

Section: Discussionmentioning

confidence: 61%

Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system

Zimmermann

Lennerz

Hein³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

207

168

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Detection and adaptation to cold temperature is crucial to survival. Cold sensing in the innocuous range of cold (>10-15°C) in the mammalian peripheral nervous system is thought to rely primarily on transient receptor potential (TRP) ion channels, most notably the menthol receptor, TRPM8. Here we report that TRP cation channel, subfamily C member 5 (TRPC5), but not TRPC1/TRPC5 heteromeric channels, are highly cold sensitive in the temperature range 37-25°C. We found that TRPC5 is present in mouse and human sensory neurons of dorsal root ganglia, a substantial number of peripheral nerves including intraepithelial endings, and in the dorsal lamina of the spinal cord that receives sensory input from the skin, consistent with a potential TRPC5 function as an innocuous cold transducer in nociceptive and thermosensory nerve endings. Although deletion of TRPC5 in 129S1/SvImJ mice resulted in no temperature-sensitive behavioral changes, TRPM8 and/or other menthol-sensitive channels appear to underpin a much larger component of noxious cold sensing after TRPC5 deletion and a shift in mechanosensitive C-fiber subtypes. These findings demonstrate that highly cold-sensitive TRPC5 channels are a molecular component for detection and regional adaptation to cold temperatures in the peripheral nervous system that is distinct from noxious cold sensing.pain | single-fiber | thermo-transient receptor potential | nociception | temperature sensing N ociceptors and thermoreceptive neurons, such as cold and heat receptors, innervate the skin and deep tissues. The cell bodies of sensory nerve endings are clustered in ganglia located in the vertebral column and cranium. Their projections extend to the skin where they arborize in terminals embedded between keratinocytes. Although nociceptors are polymodal and respond to stimuli (cold, heat, pressure, and noxious chemicals) that are capable of producing tissue damage and pain (1), cold receptors are unimodal and specialized to detect cool and cold temperatures (2). Transient receptor potential (TRP) ion channels are principal transducers of thermal stimuli that depolarize nerve terminals to the action potential threshold. Action potentials then relay the sensory information to integrative centers in the spinal cord and brain.All proteins are temperature sensitive, but most ion channels exhibit two-to threefold increases in gating with a 10°C change in temperature (Q 10 = 2-3). Certain ion channels exhibit dramatic temperature sensitivity in gating over physiologically relevant ranges (Q 10 = 10-30). Mammalian ion channels with such high Q 10 values include particular two-pore K + channels (3), the voltage-gated proton channel (4), transient receptor potential cation channel subfamily V members 1-3 (TRPV1-3) (5-7), transient receptor potential menthol receptor 8 (TRPM8) (8), and in some reports, TRP cation channel subfamily A member 1 (TRPA1) (9, 10). There is no a priori requirement for cold encoding by high Q 10 channels-action potential firing rates are affected perforce by temperature,...

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Section: Discussionmentioning

confidence: 61%

Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system

Zimmermann

Lennerz

Hein³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

207

168

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“…Recent studies, however, highlighted the limitation of using animal models in understanding human physiology (19,20). Capsaicin receptors in human sensory neurons exhibit significant heterogeneity that might reflect differences in the subunit composition (37).…”

Section: Discussionmentioning

confidence: 99%

“…rat and mouse) TRPV3 is found to express predominantly in keratinocytes (13). The difference in tissue distribution calls for caution in interpreting the applicability of behavior and knock-out studies in rodents to human physiology (19,20). Indeed, it was previously found that TRPV1 and TRPV3 subunits co-assemble into heteromeric channels (14,21).…”

mentioning

confidence: 99%

Heteromeric Heat-sensitive Transient Receptor Potential Channels Exhibit Distinct Temperature and Chemical Response

Cheng

Yang

Liu

et al. 2012

Journal of Biological Chemistry

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Background: TRPV1 and TRPV3 subunits are known to form heteromeric channels with unknown functional properties. Results: Heteromeric TRPV1/TRPV3 channels exhibit unique activation threshold temperature, dynamic range, potentiation to repetitive heating, and capsaicin sensitivity. Conclusion: Heteromeric channels are unique sensors for heat and chemical stimuli. Significance: Heteromeric channels may contribute to the fine-tuning of human sensitivity to sensory inputs.

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“…The remaining members of the TRPV subfamily (TRPV2-6) share 30-50% sequence similarity with TRPV1 (ref. 7); nevertheless they are vanilloid insensitive and play a minimal role in temperature sensation [8][9][10][11] , suggesting that 'minimal' TRPV1 is only partly representative of the other TRPV subfamily members.…”

mentioning

confidence: 99%

Structure of the Full-Length TRPV2 Channel by Cryo-EM

et al. 2016

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Transient receptor potential (TRP) proteins form a superfamily Ca 2 þ -permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a 'minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2-6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at B5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels.

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TRPV3 and TRPV4 Ion Channels are Not Major Contributors to Mouse Heat Sensation

Cited by 154 publications

References 35 publications

Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system

Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system

Heteromeric Heat-sensitive Transient Receptor Potential Channels Exhibit Distinct Temperature and Chemical Response

Structure of the Full-Length TRPV2 Channel by Cryo-EM

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