Disease relevance of TRPV3

• VRL3 responds to noxious heat with a threshold of about 39 degrees C and is co-expressed in dorsal root ganglion neurons with VR1 [1].
• We also hypothesize that closing of some TRP channels (TRPV3 and/or TRPV4) by lowering temperature may be partly responsible for the neuroprotective effect of hypothermia [2].

High impact information on TRPV3

• Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses [1].
• TRPV3 is a temperature-sensitive vanilloid receptor-like protein [1].
• VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1 [1].
• We screened a library of extracts from 50 Chinese herbal plants using a calcium-imaging assay to find compounds active on TRPV3 and TRPV4 channels [3].
• Primary keratinocytes overexpressing exogenous TRPV3 also exhibited biphasic agonist-evoked currents [4].

Biological context of TRPV3

• An amino-acid substitution at the same position in one gene was detected in DS-Nh mice and WBN/Kob-Ht rats: Gly573 to Ser (Nh mutation) or Gly573 to Cys (Ht mutation), located in the transient receptor potential (TRP) cation channel subfamily V member 3 (TRPV3) gene [5].

Anatomical context of TRPV3

• In rodents, TRPV3 and TRPV4 proteins have not been detected in sensory neurons but are highly expressed in skin epidermal keratinocytes [6].
• In addition, low levels of 2APB strongly potentiate the effect of capsaicin, protons, and heat on TRPV1 as well as that of heat on TRPV3 expressed in Xenopus oocytes [7].
• Short duration (1h) exposure of dissociated sensory neurons to NTFs increased numbers of TRPV1-positive neurons, but not of TRPV3, Nav 1.8 and IK1 and the morphological size-distribution remained similar to intact post-mortem DRG neurons [8].
• We concluded that TRPV3 was the gene responsible for Nh and Ht mutations, and that mutation in TRPV3 possibly correlated with increased mast cell numbers [5].

Associations of TRPV3 with chemical compounds

• Similar to menthol, both camphor and cinnamaldehyde (initially reported to be specific activators of TRPV3 and TRPA1, respectively) also modulate other thermoTRPs [9].
• However, human physiological studies demonstrate a paradoxical role of menthol in modulation of warm sensation, and here, we show that menthol also activates heat-activated TRPV3 [9].

Other interactions of TRPV3

• Both TRPV3 and TRPV4 are expressed in 308 cells [6].
• Minimal mRNA for TRPV3 or TRPM8 was amplified [10].

References