Changes in interstitial ATP levels and blood flow during local heating of human skin

Abstract

Heating keratinocytes is believed to activate the transient receptor potential vanilloid type III ion channel (TRPV3) resulting in the release of ATP. We examined the hypothesis that local skin heating would activate keratinocyte TRPV3 channels resulting in an increase in interstitial ATP that would contribute to a rise in skin blood flow (SkBF). Two microdialysis probes were inserted into the dermis on the dorsal aspect of the forearm in 15 young, healthy subjects. To manipulate the level of activation of TRPV3 channels the probed skin was heated to 31, 35, 39, and 43°C for 8 minutes each with an automated peltier device (3 cm x 3 cm). SkBF was monitored as cutaneous vascular conductance (CVC, %peak) and dialysate collected during each heating phase was analyzed for ATP ([ATP]d). At a skin temperature of 31°C [ATP]d averaged 21.70 ± 6.09 nM while CVC averaged 12.57 ±1.59 %peak. Heating the skin to 35°C increased CVC to 17.63 ± 1.27 %peak (p<0.05) while [ATP]d was unchanged. At skin temperatures of 39 and 43°C [ATP]d decreased significantly ( 5.88 ± 1.68, and 8.75 ± 3.44 nM respectively) (p<0.05) while CVC significantly increased to 38.90 ± 1.37 and 60.32 ± 1.95 %peak respectively (p<0.05). The low threshold of dilation (35°C) points to a possible role for the TRPV3 channels in the dilator response. However, the reduction in [ATP]d indicates that the dilator response is not likely due to ATP acting as a vasodilator substance.