Editing Epidermis (section)

====Calcium concentration====
Keratinocyte differentiation throughout the epidermis is in part mediated by a [[calcium]] gradient, increasing from the stratum basale until the outer stratum granulosum, where it reaches its maximum, and decreasing in the stratum corneum. Calcium concentration in the stratum corneum is very low in part because those relatively dry cells are not able to dissolve the ions.<ref>{{Cite journal |last=Bikle |first=Daniel D. |last2=Xie |first2=Zhongjian |last3=Tu |first3=Chia-Ling |date=July 2012 |title=Calcium regulation of keratinocyte differentiation |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC3491811/ |journal=Expert Review of Endocrinology & Metabolism |volume=7 |issue=4 |pages=461–472 |doi=10.1586/eem.12.34 |issn=1744-6651 |pmc=3491811 |pmid=23144648}}</ref> This calcium gradient parallels keratinocyte differentiation and as such is considered a key regulator in the formation of the epidermal layers.<ref name="Proksch" />

Elevation of extracellular calcium concentrations induces an increase in [[intracellular]] free calcium concentrations.<ref>{{cite journal | vauthors = Hennings H, Kruszewski FH, Yuspa SH, Tucker RW | title = Intracellular calcium alterations in response to increased external calcium in normal and neoplastic keratinocytes | journal = Carcinogenesis | volume = 10 | issue = 4 | pages = 777–780 | date = April 1989 | pmid = 2702726 | doi = 10.1093/carcin/10.4.777 }}</ref> Part of that intracellular increase comes from calcium released from intracellular stores<ref>{{cite journal | vauthors = Pillai S, Bikle DD | title = Role of intracellular-free calcium in the cornified envelope formation of keratinocytes: differences in the mode of action of extracellular calcium and 1,25 dihydroxyvitamin D3 | journal = Journal of Cellular Physiology | volume = 146 | issue = 1 | pages = 94–100 | date = January 1991 | pmid = 1990023 | doi = 10.1002/jcp.1041460113 | s2cid = 21264605 }}</ref> and another part comes from transmembrane calcium influx,<ref>{{cite journal | vauthors = Reiss M, Lipsey LR, Zhou ZL | title = Extracellular calcium-dependent regulation of transmembrane calcium fluxes in murine keratinocytes | journal = Journal of Cellular Physiology | volume = 147 | issue = 2 | pages = 281–291 | date = May 1991 | pmid = 1645742 | doi = 10.1002/jcp.1041470213 | s2cid = 25858560 }}</ref> through both calcium-sensitive [[chloride channels]]<ref>{{cite journal | vauthors = Mauro TM, Pappone PA, Isseroff RR | title = Extracellular calcium affects the membrane currents of cultured human keratinocytes | journal = Journal of Cellular Physiology | volume = 143 | issue = 1 | pages = 13–20 | date = April 1990 | pmid = 1690740 | doi = 10.1002/jcp.1041430103 | s2cid = 8072916 }}</ref> and voltage-independent cation channels permeable to calcium.<ref>{{cite journal | vauthors = Mauro TM, Isseroff RR, Lasarow R, Pappone PA | title = Ion channels are linked to differentiation in keratinocytes | journal = The Journal of Membrane Biology | volume = 132 | issue = 3 | pages = 201–209 | date = March 1993 | pmid = 7684087 | doi = 10.1007/BF00235738 | s2cid = 13063458 }}</ref> Moreover, it has been suggested that an extracellular calcium-sensing [[cell surface receptor|receptor]] (CaSR) also contributes to the rise in intracellular calcium concentration.<ref>{{cite journal | vauthors = Tu CL, Oda Y, Bikle DD | title = Effects of a calcium receptor activator on the cellular response to calcium in human keratinocytes | journal = The Journal of Investigative Dermatology | volume = 113 | issue = 3 | pages = 340–345 | date = September 1999 | pmid = 10469331 | doi = 10.1046/j.1523-1747.1999.00698.x | doi-access = free }}</ref>