Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling
- Medical College of Wisconsin, United States
Abstract
The first point of our body's contact with tactile stimuli (innocuous and noxious) is the epidermis, the outermost layer of skin that is largely composed of keratinocytes. Here, we sought to define the role that keratinocytes play in touch sensation in vivo and ex vivo. We show that optogenetic inhibition of keratinocytes decreases behavioral and cellular mechanosensitivity. These processes are inherently mediated by ATP signaling, as demonstrated by complementary cutaneous ATP release and degradation experiments. Specific deletion of P2X4 receptors in sensory neurons markedly decreases behavioral and primary afferent mechanical sensitivity, thus positioning keratinocyte-released ATP to sensory neuron P2X4 signaling as a critical component of baseline mammalian tactile sensation. These experiments lay a vital foundation for subsequent studies into the dysfunctional signaling that occurs in cutaneous pain and itch disorders, and ultimately, the development of novel topical therapeutics for these conditions.
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Author details
Funding
National Institute of Neurological Disorders and Stroke (NS040538)
- Cheryl L Stucky
National Institute of Neurological Disorders and Stroke (NS070711)
- Cheryl L Stucky
Advancing a Healthier Wisconsin Endowment
- Cheryl L Stucky
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All of the animal procedures strictly adhered to the NIH Guide for the Care and Use of Laboratory animals, and were performed in accordance with the Institutional Animal Care and Use Committee at the Medical College of Wisconsin (approval #: 0383).
Copyright
© 2018, Moehring et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling
eLife 7:e31684.
https://doi.org/10.7554/eLife.31684
