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Mechanical stimulus-evoked signal transduction between keratinocytes and sensory neurons via extracellular ATP
- Source :
- Biochemical and biophysical research communications. 582
- Publication Year :
- 2021
-
Abstract
- The skin is exposed to various external stimuli. Keratinocytes, which are the main cell type in the epidermis, interact with peripheral sensory neurons and modulate neuronal activity. Recent studies have revealed that keratinocytes play crucial roles in nociception, and that ATP is one of the main mediators of signal transduction from keratinocytes to sensory neurons. However, no quantitative cellular level analyses of ATP-mediated information flow from keratinocytes to sensory dorsal root ganglion (DRG) neurons have been conducted. In this study, we performed simultaneous imaging of cell surface ATP and intracellular Ca2+ signals using both iATPSnFR, a genetically encoded ATP probe localized to the outside of the cell membrane, and the Ca2+ probe, Fura-red. Upon mechanical stimulation of the keratinocyte with a glass needle, an increase in Ca2+ and ATP release were observed around the stimulated area, and these phenomena were positively correlated. In cultured DRG neurons and keratinocytes neighboring the stimulated keratinocyte, increased intracellular Ca2+ concentration and levels of cell surface ATP on the side closer to the stimulated cell were detected. The ratio of Ca2+ response to input ATP signal was significantly larger in DRG neurons than in keratinocytes. We found that DRG neurons were more sensitive to ATP than keratinocytes, and therefore, only DRG neurons responded to ATP at 1 μM or lower concentrations when in co-culture with keratinocytes. Moreover, signals caused by moderate mechanical stimulation of keratinocytes were transmitted predominantly to DRG neurons. These findings would be important in the further determination of the detailed mechanism of nociception in the epidermis.
- Subjects :
- Keratinocytes
Nociception
Sensory Receptor Cells
Cations, Divalent
Biophysics
Stimulation
Biochemistry
Mechanotransduction, Cellular
Time-Lapse Imaging
Cell membrane
Adenosine Triphosphate
Dorsal root ganglion
Genes, Reporter
Ganglia, Spinal
medicine
Extracellular
Premovement neuronal activity
Animals
Humans
Rats, Wistar
Molecular Biology
Benzofurans
Chemistry
Cell Membrane
Imidazoles
Infant, Newborn
Cell Biology
Coculture Techniques
Cell biology
Rats
medicine.anatomical_structure
nervous system
Molecular Probes
Calcium
Signal transduction
Epidermis
Keratinocyte
Intracellular
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 582
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....e2127fc8cf8f6cf5f92a61d643a64f06