Mechanosensory and ATP Release Deficits following Keratin14-Cre-Mediated TRPA1 Deletion Despite Absence of TRPA1 in Murine Keratinocytes

Keratinocytes are the first cells that come into direct contact with external tactile stimuli; however, their role in touch transduction in vivo is not clear. The ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) is essential for some mechanically-gated currents in sensory neurons, amplifie...

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Published in:	PloS one 2016-03, Vol.11 (3), p.e0151602
Main Authors:	Zappia, Katherine J, Garrison, Sheldon R, Palygin, Oleg, Weyer, Andy D, Barabas, Marie E, Lawlor, Michael W, Staruschenko, Alexander, Stucky, Cheryl L
Format:	Article
Language:	eng
Subjects:	Adenosine Triphosphate - metabolism Afferent Pathways - physiology Anatomy & physiology Animals Animals, Congenic Ankyrin Ankyrins Arthritis, Experimental - physiopathology ATP Biology Biology and Life Sciences Clonal deletion Epidermal Cells Epidermis Epidermis - metabolism Freund's Adjuvant - toxicity Gene deletion Gene Expression Profiling Gene Knockdown Techniques Genes, Reporter Integrases Ion channels Keratin Keratinocytes Keratinocytes - metabolism Mechanoreceptors - physiology Mechanotransduction Mechanotransduction, Cellular - physiology Medicine and Health Sciences Mice Mice, Inbred C57BL Nervous system Neurobiology Neurosciences Nociception - physiology Organ Specificity Pain Pain Threshold - physiology Physical Stimulation - adverse effects Physiological aspects Physiology Risk factors RNA, Messenger - biosynthesis Rodents Sensory neurons Sensory Receptor Cells - physiology Skin Skin - cytology Skin - embryology Tactile stimuli Touch Transient Receptor Potential Channels - biosynthesis Transient Receptor Potential Channels - deficiency Transient Receptor Potential Channels - genetics Transient Receptor Potential Channels - physiology Transient receptor potential proteins TRPA1 Cation Channel
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Summary:	Keratinocytes are the first cells that come into direct contact with external tactile stimuli; however, their role in touch transduction in vivo is not clear. The ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) is essential for some mechanically-gated currents in sensory neurons, amplifies mechanical responses after inflammation, and has been reported to be expressed in human and mouse skin. Other reports have not detected Trpa1 mRNA transcripts in human or mouse epidermis. Therefore, we set out to determine whether selective deletion of Trpa1 from keratinocytes would impact mechanosensation. We generated K14Cre-Trpa1fl/fl mice lacking TRPA1 in K14-expressing cells, including keratinocytes. Surprisingly, Trpa1 transcripts were very poorly detected in epidermis of these mice or in controls, and detection was minimal enough to preclude observation of Trpa1 mRNA knockdown in the K14Cre-Trpa1fl/fl mice. Unexpectedly, these K14Cre-Trpa1fl/fl mice nonetheless exhibited a pronounced deficit in mechanosensitivity at the behavioral and primary afferent levels, and decreased mechanically-evoked ATP release from skin. Overall, while these data suggest that the intended targeted deletion of Trpa1 from keratin 14-expressing cells of the epidermis induces functional deficits in mechanotransduction and ATP release, these deficits are in fact likely due to factors other than reduction of Trpa1 expression in adult mouse keratinocytes because they express very little, if any, Trpa1.
ISSN:	1932-6203 1932-6203