Ca2+ waves in keratinocytes are transmitted to sensory neurons: The involvement of extracellular ATP and P2Y2 receptor activation

Schuichi Koizumi, Kayoko Fujishita, Kaori Inoue, Yukari Shigemoto-Mogami, Tsuda Makoto, Kazuhide Inoue

Research output: Contribution to journalArticle

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Abstract

ATP acts as an intercellular messenger in a variety of cells. In the present study, we have characterized the propagation of Ca2+ waves mediated by extracellular ATP in cultured NHEKs (normal human epidermal keratinocytes) that were co-cultured with mouse DRG (dorsal root ganglion) neurons. Pharmacological characterization showed that NHEKs express functional metabotropic P2Y2 receptors. When a cell was gently stimulated with a glass pipette, an increase in [Ca2+]i (intracellular Ca2+ concentration) was observed, followed by the induction of propagating Ca2+ waves in neighbouring cells in an extracellular ATP-dependent manner. Using an ATP-imaging technique, the release and diffusion of ATP in NHEKs were confirmed. DRG neurons are known to terminate in the basal layer of keratinocytes. In a coculture of NHEKs and DRG neurons, mechanical-stimulation-evoked Ca2+ waves in NHEKs caused an increase in [Ca2+]i in the adjacent DRG neurons, which was also dependent on extracellular ATP and the activation of P2Y2 receptors. Taken together, extracellular ATP is a dominant messenger that forms intercellular Ca2+ waves in NHEKs. In addition, Ca2+ waves in NHEKs could cause an increase in [Ca2+]i in DRG neurons, suggesting a dynamic cross-talk between skin and sensory neurons mediated by extracellular ATP.

Original languageEnglish
Pages (from-to)329-338
Number of pages10
JournalBiochemical Journal
Volume380
Issue number2
DOIs
Publication statusPublished - Jun 1 2004

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Purinergic P2Y2 Receptors
Purinergic P2 Receptors
Sensory Receptor Cells
Keratinocytes
Neurons
Adenosine Triphosphate
Chemical activation
Spinal Ganglia
Coculture Techniques
Glass
Skin
Pharmacology
Imaging techniques

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Ca2+ waves in keratinocytes are transmitted to sensory neurons : The involvement of extracellular ATP and P2Y2 receptor activation. / Koizumi, Schuichi; Fujishita, Kayoko; Inoue, Kaori; Shigemoto-Mogami, Yukari; Makoto, Tsuda; Inoue, Kazuhide.

In: Biochemical Journal, Vol. 380, No. 2, 01.06.2004, p. 329-338.

Research output: Contribution to journalArticle

Koizumi, Schuichi ; Fujishita, Kayoko ; Inoue, Kaori ; Shigemoto-Mogami, Yukari ; Makoto, Tsuda ; Inoue, Kazuhide. / Ca2+ waves in keratinocytes are transmitted to sensory neurons : The involvement of extracellular ATP and P2Y2 receptor activation. In: Biochemical Journal. 2004 ; Vol. 380, No. 2. pp. 329-338.
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