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The skin is our largest organ serving different tasks from barrier formation through somatosensing to hair development. Recently, members of the large trp (Transient Receptor Potential, TRP) gene family encoding proteins that form cation selective ion channel have been identified to play a crucial role in skin functions. Within the 28 different mammalian TRP channels, TRPV3 might be the most important member in the skin. This review gives an overview on functional properties of TRPV3 in skin physiology and in certain skin diseases. TRP channels: an introductionIn 1969, a Drosophila mutant was discovered which was defective in light sensing and exhibited only transient light-induced receptor potentials (TRP) instead the normal maintained response (1). This finding was explained by a defect in an ion channel and triggered the discovery of the trp gene family which encodes TRP channels (for the history of this discovery see (2-4)). The TRP channel superfamily contains 28 mammalian members (27 in human) subdivided in six subfamilies which all permeate cations (5,6). TRP channels -which probably function mostly as hetero-or homotetramers (7,8) (more detailed information see in TRP channel data base Clapham/Owsianik/Nilius (9)) -are located in the plasma membrane (PM) as cation entry pores and generate upon activation cell depolarization; this can result in activation or inactivation of voltage-dependent ion channels, thereby modulating the driving force of ion flux through channels and transporters. Some TRPs also act as intracellular ion channels, mainly as Ca 2+ release channels, in several cell organelles such as lysosomes, endosomes, Golgi network, endoplasmic reticulum and synaptic vesicles (10). TRPV familyMembers of the TRPV (vanilloid) family comprise six ion channels based on homology. Four groups can be identified: TRPV1/ TRPV2, TRPV3, TRPV4, and TRPV5/6. This family is named after the first mammalian member of the TRPV subfamily, which binds vanilloids (e.g. capsaicin) and was first coined as vanilloid receptor-1 (VR1) (6,11). Members of the TRPV family function as homo and/or heterotetrameric complexes but can also heteromultimerize with other TRP channels such as TRPC1 and TRPP2 (7,12,13).Among the TRPVs channels, TRPV1, 2, 3 and 4 have striking temperature sensitivities. Indeed, TRPV1 is activated at >43°C; TRPV2 at >52°C; TRPV3 at >33°C; and TRPV4 at >30°C (14). These thermo-TRPVs are modestly permeable to Ca 2+ , whereas TRPV5 and TRPV6 are the only highly Ca 2+ selective channels in the TRP family. Nevertheless, functions of all of these channels are tightly regulated by the intracellular Ca 2+ concentration ([Ca 2+ ] i ) and phosphoinositides (15).With respect to skin physiology and pathophysiology, probably TRPV3 is the most important TRPV channel. Therefore, the cutaneous role of TRPV3 will be detailed in this review.

Section: Skin Inflammationmentioning

confidence: 96%

Section: Pruriceptive Itchmentioning

confidence: 99%

TRPV3: a ‘more than skinny’ channel

Nilius

Bı́ró

2013

“…Another thermosensitive transient receptor potential channel, which has been shown to have a role in itch in mice, is TRPV3 (92). TRPV3 is abundantly expressed in keratinocytes and scalp HF, mainly the ORS (93)(94)(95).…”

Section: Trpv1mentioning

confidence: 99%

The itchy scalp - scratching for an explanation

Saif

Ericson

Yosipovitch

2011

Scalp pruritus is a common complaint that is considered a diagnostically and therapeutically challenging situation. Scalp skin has a unique neural structure that contains densely innervated hair follicles and dermal vasculature. In spite of the recent advances in our understanding of itch pathophysiology, scalp itching has not been studied as yet. In this review, we summarize the current knowledge on the neurobiology of scalp and hair follicles as well as itch mediators and provide a putative mechanism for scalp itch with special emphasis on neuroanatomy and pathophysiology.

“…SP-induced itch is diminished in TRPA1 deficient mice underscoring the role of TRP channels not only in the release of SP, but also in transmission of SPinduced itch (68). TRPV3 mediates itch at the level of keratinocytes and overexpression of TRPV3 in both human (Olmsted syndrome) and rodents is associated with itch and atopic dermatitis-like skin changes (69)(70)(71).…”

Section: Endovanilloidsmentioning

confidence: 99%

Are itch and scratching the nausea and vomiting of skin?

Ostadhadi

Azimi

Lerner

et al. 2016

The physiologic similarities between itch and nausea may not be evident initially, but they share the role of repelling irritants and toxins from the body by inducting scratching and vomiting, respectively. In addition, itch and nausea frequently occur together in certain conditions such as uraemia. Here we show that the mechanisms underlying itch and nausea overlap and that advances in either field may influence the identification of novel drug targets, particularly for itch.