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TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP Mandadi S; Sokabe T; Shibasaki K; Katanosaka K; Mizuno A; Moqrich A; Patapoutian A; Fukumi-Tominaga T; Mizumura K; Tominaga MPflugers Arch 2009[Oct]; 458 (6): 1093-102Transient 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.|Adenosine Triphosphate/*physiology[MESH]|Animals[MESH]|Calcium/metabolism[MESH]|Cells, Cultured[MESH]|Coculture Techniques[MESH]|Ganglia, Spinal/cytology[MESH]|Glutamic Acid/metabolism[MESH]|Hot Temperature[MESH]|Humans[MESH]|Keratinocytes/*physiology[MESH]|Male[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Patch-Clamp Techniques[MESH]|Sensory Receptor Cells/*metabolism[MESH]|Serotonin/metabolism[MESH]|Signal Transduction/physiology[MESH]|Skin/metabolism[MESH]|TRPV Cation Channels/*physiology[MESH] |
