Our understanding of how the mammalian somatosensory system detects noxious cold is still limited. While the role of TRPM8 in signaling mild non-noxious coolness is reasonably understood, the molecular identity of channels transducing painful cold stimuli remains unresolved. TRPC5 was originally described to contribute to moderate cold responses of dorsal root ganglia neurons in vitro, but mice lacking TRPC5 exhibited no change in behavioral responses to cold temperature. The question of why a channel endowed with the ability to be activated by cooling contributes to the cold response only under certain conditions is currently being intensively studied. It seems increasingly likely that the physiological detection of cold temperatures involves multiple different channels and mechanisms that modulate the threshold and intensity of perception. In this review, we aim to outline how TRPC5 may contribute to these mechanisms and what molecular features are important for its role as a cold sensor.
- MeSH
- kationtové kanály TRPC * metabolismus MeSH
- kationtové kanály TRPM metabolismus MeSH
- lidé MeSH
- myši MeSH
- nízká teplota * MeSH
- spinální ganglia metabolismus fyziologie MeSH
- vnímání teploty * fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Klíčová slova
- senzitivní dráhy,
- MeSH
- čití, cítění * fyziologie MeSH
- lidé MeSH
- mechanoreceptory fyziologie MeSH
- nervové dráhy anatomie a histologie fyziologie MeSH
- nocicepce fyziologie MeSH
- propriocepce fyziologie MeSH
- vnímání teploty fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Numerous physiological functions rely on distinguishing temperature through temperature-sensitive transient receptor potential channels (thermo-TRPs). Although the function of thermo-TRPs has been studied extensively, structural determination of their heat- and cold-activated states has remained a challenge. Here, we present cryo-EM structures of the nanodisc-reconstituted wild-type mouse TRPV3 in three distinct conformations: closed, heat-activated sensitized and open states. The heat-induced transformations of TRPV3 are accompanied by changes in the secondary structure of the S2-S3 linker and the N and C termini and represent a conformational wave that links these parts of the protein to a lipid occupying the vanilloid binding site. State-dependent differences in the behavior of bound lipids suggest their active role in thermo-TRP temperature-dependent gating. Our structural data, supported by physiological recordings and molecular dynamics simulations, provide an insight for understanding the molecular mechanism of temperature sensing.
- MeSH
- buněčné linie MeSH
- elektronová kryomikroskopie MeSH
- gating iontového kanálu MeSH
- HEK293 buňky MeSH
- kationtové kanály TRPV metabolismus MeSH
- konformace proteinů MeSH
- lidé MeSH
- lipidy chemie MeSH
- myši MeSH
- nízká teplota MeSH
- termodynamika MeSH
- vazba proteinů fyziologie MeSH
- vnímání teploty fyziologie MeSH
- vysoká teplota MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
The discovery of the role of the transient receptor potential ankyrin 1 (TRPA1) channel as a polymodal detector of cold and pain-producing stimuli almost two decades ago catalyzed the consequent identification of various vertebrate and invertebrate orthologues. In different species, the role of TRPA1 has been implicated in numerous physiological functions, indicating that the molecular structure of the channel exhibits evolutionary flexibility. Until very recently, information about the critical elements of the temperature-sensing molecular machinery of thermosensitive ion channels such as TRPA1 had lagged far behind information obtained from mutational and functional analysis. Current developments in single-particle cryo-electron microscopy are revealing precisely how the thermosensitive channels operate, how they might be targeted with drugs, and at which sites they can be critically regulated by membrane lipids. This means that it is now possible to resolve a huge number of very important pharmacological, biophysical and physiological questions in a way we have never had before. In this review, we aim at providing some of the recent knowledge on the molecular mechanisms underlying the temperature sensitivity of TRPA1. We also demonstrate how the search for differences in temperature and chemical sensitivity between human and mouse TRPA1 orthologues can be a useful approach to identifying important domains with a key role in channel activation.
- MeSH
- ankyriny genetika fyziologie MeSH
- kationtový kanál TRPA1 genetika fyziologie MeSH
- lidé MeSH
- myši MeSH
- nízká teplota MeSH
- vnímání teploty genetika fyziologie MeSH
- vysoká teplota MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Long term follow-up of face transplant patients is fundamental to our understanding of risks and benefits of this procedure. Worldwide experience has shown that function improves gradually over time. METHODS: In April of 2009, a multidisciplinary team at Brigham and Women's Hospital performed face transplantation on a male patient to address a severe facial defect caused by high-voltage burns. Physical and occupational therapy was performed for the first six post-operative months. Close monitoring of the patient's functional recovery, immunosuppression, and quality of life was performed at set time points. RESULTS: Three years after face transplantation, the patient has recovered near-normal sensation. Along with satisfactory aesthetic results, his motor function continues to improve, aiding his speech, facial expressions, and social interaction. Furthermore, the patient reports continued improvements in quality of life. Infectious, metabolic, and immunologic complications have been successfully managed in a team approach. Immunosuppression doses have been effectively reduced, and steroid therapy was withdrawn before the end of the first postoperative year. CONCLUSIONS: The presented outcomes demonstrate the procedure's growing role in reconstructive surgery as teams continue to focus their efforts on further optimization of immunosuppression and surgical technique.
- MeSH
- alografty MeSH
- hmat fyziologie MeSH
- imunosupresivní léčba MeSH
- kosterní svaly fyziologie MeSH
- kvalita života MeSH
- lidé MeSH
- následné studie MeSH
- obličej fyziologie MeSH
- obnova funkce * MeSH
- poranění obličeje chirurgie MeSH
- transplantace obličeje * škodlivé účinky MeSH
- vnímání teploty fyziologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Topically applied camphor elicits a sensation of cool, but nothing is known about how it affects cold temperature sensing. We found that camphor sensitizes a subpopulation of menthol-sensitive native cutaneous nociceptors in the mouse to cold, but desensitizes and partially blocks heterologously expressed TRPM8 (transient receptor potential cation channel subfamily M member 8). In contrast, camphor reduces potassium outward currents in cultured sensory neurons and, in cold nociceptors, the cold-sensitizing effects of camphor and menthol are additive. Using a membrane potential dye-based screening assay and heterologously expressed potassium channels, we found that the effects of camphor are mediated by inhibition of Kv7.2/3 channels subtypes that generate the M-current in neurons. In line with this finding, the specific M-current blocker XE991 reproduced the cold-sensitizing effect of camphor in nociceptors. However, the M-channel blocking effects of XE991 and camphor are not sufficient to initiate cold transduction but require a cold-activated inward current generated by TRPM8. The cold-sensitizing effects of XE991 and camphor are largest in high-threshold cold nociceptors. Low-threshold corneal cold thermoreceptors that express high levels of TRPM8 and lack potassium channels are not affected by camphor. We also found that menthol--like camphor--potently inhibits Kv7.2/3 channels. The apparent functional synergism arising from TRPM8 activation and M-current block can improve the effectiveness of topical coolants and cooling lotions, and may also enhance TRPM8-mediated analgesia.
- MeSH
- kafr farmakologie MeSH
- kationtové kanály TRPM genetika metabolismus MeSH
- menthol farmakologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nervová vlákna nemyelinizovaná účinky léků metabolismus MeSH
- nízká teplota MeSH
- nociceptory metabolismus fyziologie MeSH
- signální transdukce účinky léků fyziologie MeSH
- spinální ganglia účinky léků metabolismus MeSH
- termoreceptory metabolismus fyziologie MeSH
- vnímání teploty účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Piezosurgery is a promising meticulous system for bone cutting, based on ultrasound microvibrations. It is thought that the impact of piezosurgery on the integrity of soft tissue is generally low, but it has not been examined critically. The authors undertook an experimental study to evaluate the brain tissue response to skull bone removal using piezosurgery compared with a conventional drilling method. In Wistar male rats, a circular bone window was drilled to the parietal bone using piezosurgery on one side and a conventional bone drill on the other side. The behavioural performance of animals was evaluated using the motor BBB test and sensory plantar test. The brains of animals were evaluated by magnetic resonance imaging (MRI) and histology. The results of MRI showed significantly increased depth and width of the brain lesion in the region of conventional drilling compared with the region where piezosurgery was used. Cresylviolet and NF 160 staining confirmed these findings. There was no significant difference in any of the behavioural tests between the two groups. In conclusion, piezosurgery is a safe method for the performance of osteotomy in close relation to soft tissue, including an extremely injury-sensitive tissue such as brain.
- MeSH
- astrocyty patologie MeSH
- barvicí látky diagnostické užití MeSH
- časové faktory MeSH
- chování zvířat fyziologie MeSH
- krysa rodu rattus MeSH
- lokomoce fyziologie MeSH
- magnetická rezonanční tomografie MeSH
- mozek patologie MeSH
- náhodné rozdělení MeSH
- neurofilamentové proteiny analýza MeSH
- osteotomie přístrojové vybavení metody MeSH
- oxaziny diagnostické užití MeSH
- peroperační komplikace prevence a kontrola MeSH
- piezochirurgie přístrojové vybavení metody MeSH
- pohybová aktivita fyziologie MeSH
- poranění mozku prevence a kontrola MeSH
- potkani Wistar MeSH
- temenní kost chirurgie MeSH
- vnímání teploty fyziologie MeSH
- zadní končetina fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Cílem práce je poukázat na význam kožní termometrie v diagnostice sekundárního Raynaudova syndromu z vibrací. Autor porovnává kožní teploty pacientů s Raynaudovým syndromem. Pacienti byli rozděleni na skupiny 1, 2 a 3 – od nejlehčí po nejtěžší stupeň onemocnění – a kontrolní skupinu, a to nativně a v 0. a 20. minutě po chladovém testu. Ke statistickým výpočtům a srovnáním byla použita hodnota mediánu kožních teplot z osmi měřených prstů.
The aim of the paper is to describe the significance of skin termometry in diagnostics of the secondary Raynaud syndrome from vibrations. Skin temperatures of patients with the Raynaud syndrome – divided to groups No. 1, 2 and 3 according to the results of plethysmography – will be compared to a control group, at 0 and 20th minute after a chill test. The value of median of skin temperatures of 8 measured fingers is used for the statistical analysis and comparisons.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci z povolání diagnóza klasifikace MeSH
- pletysmografie využití MeSH
- Raynaudova nemoc diagnóza klasifikace MeSH
- stupeň závažnosti nemoci MeSH
- vibrace škodlivé účinky MeSH
- vnímání teploty fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
Public Health Service publication ; no. 1084 Public health monograph ; no. 72
viii, 35 s. : tab., grafy ; 26 cm
- MeSH
- nízká teplota MeSH
- termoregulace fyziologie MeSH
- vnímání teploty fyziologie MeSH
- vysoká teplota MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Fyziologie člověka a srovnávací fyziologie
- NLK Obory
- fyziologie