title: Ryanodine receptors are expressed in epidermal keratinocytes and associated with keratinocyte differentiation and epidermal permeability barrier homeostasis.
abstract: Ryanodine receptors (RyRs) have an important role as calcium channels in the regulation of intracellular calcium levels in the nervous system and muscle. In the present study, we investigated the expression of RyR in human epidermis. Immunohistochemical studies and reverse transcription-PCR indicated the expression of RyR type 1, 2, and 3 proteins in epidermal keratinocytes. The expression level of each RyR subtype was higher in differentiating keratinocytes than in proliferative cells. We also demonstrated the functional expression of RyR by calcium imaging. In cultured human keratinocytes, application of the RyR agonist 4-chloro-m-cresol (CMC) induced elevation of the intracellular calcium concentration, and co-application of the RyR antagonist 1,1'-diheptyl-4,4'-bipyridinium dibromide (DHBP) blocked the elevation. Application of CMC accelerated keratinocyte differentiation in vitro. On the other hand, topical application of CMC after tape-stripping of hairless mouse skin delayed barrier recovery, whereas application of an RyR antagonist, dantrolene or DHBP, accelerated the barrier recovery. These results suggest that RyR expressed in epidermal keratinocytes is associated with both differentiation of keratinocytes and epidermal barrier homeostasis.
authors: Shiseido Innovative Science Research and Development Center, Yokohama, Japan. sumiko.denda@to.shiseido.co.jp
authors: Sumiko
authors: S
authors: Denda
authors: Junichi
authors: J
authors: Kumamoto
authors: Kentaro
authors: K
authors: Takei
authors: Moe
authors: M
authors: Tsutsumi
authors: Hirofumi
authors: H
authors: Aoki
authors: Mitsuhiro
authors: M
authors: Denda
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003408:Cresols / Q000494:pharmacology; D000078404:Epidermal Cells; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D010539:Permeability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*; D014755:Viologens / Q000494:pharmacology
chemical_list: C523784:1,1'-diheptyl-4,4'-bipyridinium; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D003408:Cresols; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D014755:Viologens; C006984:chlorocresol; D002118:Calcium