CHANGES IN CALCIUM RESPONSIVENESS AND HANDLING DURING KERATINOCYTE DIFFERENTIATION - POTENTIAL ROLE OF THE CALCIUM RECEPTOR

Citation
Dd. Bikle et al., CHANGES IN CALCIUM RESPONSIVENESS AND HANDLING DURING KERATINOCYTE DIFFERENTIATION - POTENTIAL ROLE OF THE CALCIUM RECEPTOR, The Journal of clinical investigation, 97(4), 1996, pp. 1085-1093
Citations number
40
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
00219738
Volume
97
Issue
4
Year of publication
1996
Pages
1085 - 1093
Database
ISI
SICI code
0021-9738(1996)97:4<1085:CICRAH>2.0.ZU;2-U
Abstract
Extracellular calcium concentrations (Cao) > 0.1 mM are required for t he differentiation of normal human keratinocytes in culture. Increment s in Cao result in acute and sustained increases in the intracellular calcium level (Cai), postulated to involve both a release of calcium f rom intracellular stores and a subsequent increase in calcium influx t hrough nonspecific cation channels. The sustained rise in Cai appears to be necessary for keratinocyte differentiation. To understand the me chanism by which keratinocytes respond to Cao, we measured the acute e ffects of Cao on Cai and calcium influx in keratinocytes at various st ages of differentiation. We then demonstrated the existence of the cal cium receptor (CaR) in keratinocytes and determined the effect of calc ium-induced differentiation on its mRNA levels. Finally, we examined t he role of Cai in regulating both the initial rise in Cai after the sw itch to higher Cao and the activity of the nonspecific cation channel through which calcium influx occurs. Our data indicate that the acute Cai response to Cao is lost as the cells differentiate and increase th eir basal Cai. These data correlated with the decrease in CaR mRNA lev els in cells grown in low calcium. However, calcium influx as measured by Ca-45 uptake increased with differentiation in 1.2 mM calcium, con sistent with the increase in CaR mRNA in these cells as well as the ca lcium-induced opening of the nonspecific cation channels. We conclude that the keratinocyte contains a CaR that regulates both the initial r elease of Cai from intracellular stores and the subsequent increase in calcium flux through nonspecific calcium channels. A rising level of Cai may turn off the release of calcium from intracellular stores whil e potentiating the influx through the nonspecific cation channels. Dif ferentiation of keratinocytes appears to increase the CaR, which may f acilitate the maintenance of the high Cai required for differentiation .