Skin blood flow (SKBF) demonstrates a biphasic response to innocuous, local heating. Much about the mechanism of the first phase is unknown. A type of ion channel (TRPV3) sensitive to and increasingly activated by temperatures from ~33 to ~45°C may be involved. TRPV3 channels are abundantly located in the keratinocytes and are believed to elicit the release of ATP, a putative cutaneous vasodilator, upon activation. This study investigated the possibility that TRPV3 channels and ATP have a role in the first phase of the SBKF response to local heat. Fifteen young, healthy subjects participated in the study. Two microdialysis probes were inserted into the dermis on the forearm. Using a peltier module, the skin above the probes (3cm x 3cm) was heated to 31, 35, 39, and 43°C to manipulate the level of activation of TRPV3 channels for eight minutes each. The probes were perfused with 0.9% saline at 2µl/min. Dialysate from each phase was analyzed for the concentration of ATP ([ATP]d). Cutaneous vascular conductance (CVC), measured by laser Doppler flowmetry, was monitored throughout. The [ATP]d decreased significantly when the skin was heated to temperatures known to strongly activate TRPV3 channels (i.e 39 and 43°C). [ATP]d demonstrated no relationship with CVC and only a very weak relationship with peltier temperature (r2 = 0.02, p<0.05). These data indicate that local heating and presumably heat-induced activation of the TRPV3 channels results in the decrease, not increase, of the release of ATP in human skin, and that the [ATP]d is not related to changes in skin blood flow. Significant dilation was observed at 35°C. This threshold, which is several degrees lower than the threshold previously reported, suggests that the TRPV3 channels may be involved in the dilator response in some way independent of interstitial ATP.



College and Department

Life Sciences; Exercise Sciences



Date Submitted


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hyperemia, thermosensation, axon reflex