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TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP

2009; Springer Science+Business Media; Volume: 458; Issue: 6 Linguagem: Inglês

10.1007/s00424-009-0703-x

1432-2013

Sravan Mandadi, Takaaki Sokabe, Koji Shibasaki, Kimiaki Katanosaka, Atsuko Mizuno, Aziz Moqrich, Ardem Patapoutian, Tomoko Fukumi‐Tominaga, Kazue Mizumura, Makoto Tominaga,

Pain Mechanisms and Treatments

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.