TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP.
Transient receptor potential V3 (TRPV3) and TRPV4 are heat-activated cation channels expressed in keratinocytes. It has been proposed that heat-activation of TRPV3 and/or TRPV4 in the skin may release diffusible molecules which would then activate termini of neighboring dorsal root ganglion (DRG) neurons. Here we show that adenosine triphosphate (ATP) is such a candidate molecule released from keratinocytes upon heating in the co-culture systems. Using TRPV1-deficient DRG neurons, we found that increase in cytosolic Ca(2+)-concentration in DRG neurons upon heating was observed only when neurons were co-cultured with keratinocytes, and this increase was blocked by P2 purinoreceptor antagonists, PPADS and suramin. In a co-culture of keratinocytes with HEK293 cells (transfected with P2X(2) cDNA to serve as a bio-sensor), we observed that heat-activated keratinocytes secretes ATP, and that ATP release is compromised in keratinocytes from TRPV3-deficient mice. This study provides evidence that ATP is a messenger molecule for mainly TRPV3-mediated thermotransduction in skin.
Mandadi
Sravan
S
Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institute for Physiological Sciences, Okazaki, Japan.
Sokabe
Takaaki
T
Shibasaki
Koji
K
Katanosaka
Kimiaki
K
Mizuno
Atsuko
A
Moqrich
Aziz
A
Patapoutian
Ardem
A
Fukumi-Tominaga
Tomoko
T
Mizumura
Kazue
K
Tominaga
Makoto
M
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D005727:Ganglia, Spinal / Q000166:cytology; D018698:Glutamic Acid / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism; D050916:TRPV Cation Channels / Q000502:physiology*
D050916:TRPV Cation Channels; C486760:Trpv3 protein, mouse; D012701:Serotonin; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D002118:Calcium