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. 1992 Feb;89(2):530–538. doi: 10.1172/JCI115617

Calcium and potassium are important regulators of barrier homeostasis in murine epidermis.

S H Lee 1, P M Elias 1, E Proksch 1, G K Menon 1, M Mao-Quiang 1, K R Feingold 1
PMCID: PMC442884  PMID: 1737844

Abstract

Topical solvent treatment removes lipids from the stratum corneum leading to a marked increase in transepidermal water loss (TEWL). This disturbance stimulates a variety of metabolic changes in the epidermis leading to rapid repair of the barrier defect. Using an immersion system we explored the nature of the signal leading to barrier repair in intact mice. Initial experiments using hypotonic to hypertonic solutions showed that water transit per se was not the crucial signal. However, addition of calcium at concentrations as low as 0.01 mM inhibited barrier repair. Moreover, both verapamil and nifedipine, which block calcium transport into cells, prevented the calcium-induced inhibition of TEWL recovery. Additionally, trifluoroperazine or N-6-aminohexyl-5-chloro-1-naphthalenesulfonamide, which inhibit calmodulin, prevented the calcium-induced inhibition of TEWL recovery. Although these results suggest an important role for calcium in barrier homeostasis, calcium alone was only modestly effective in inhibiting TEWL recovery. Potassium alone (10 mM) and phosphate alone (5 mM) also produced a modest inhibition of barrier repair. Together, however, calcium and potassium produced a synergistic inhibition of barrier repair (control 50% recovery vs. calcium + potassium 0-11% recovery in 2.5 h). Furthermore, in addition to inhibiting TEWL recovery, calcium and potassium also prevented the characteristic increase in 3-hydroxy-3-glutaryl CoA reductase activity that occurs after barrier disruption. Finally, the return of lipids to the stratum corneum was also blocked by calcium and potassium. These results demonstrate that the repair of the epidermal permeability barrier after solvent disruption can be prevented by calcium, potassium, and phosphate. The repair process may be signalled by a decrease in the concentrations of these ions in the upper epidermis resulting from increased water flux leading to passive loss of these ions.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brown E. M. Extracellular Ca2+ sensing, regulation of parathyroid cell function, and role of Ca2+ and other ions as extracellular (first) messengers. Physiol Rev. 1991 Apr;71(2):371–411. doi: 10.1152/physrev.1991.71.2.371. [DOI] [PubMed] [Google Scholar]
  2. Dykes P. J., Jenner L. A., Marks R. The effect of calcium on the initiation and growth of human epidermal cells. Arch Dermatol Res. 1982;273(3-4):225–231. doi: 10.1007/BF00409250. [DOI] [PubMed] [Google Scholar]
  3. Elias P. M., Feingold K. R. Lipid-related barriers and gradients in the epidermis. Ann N Y Acad Sci. 1988;548:4–13. doi: 10.1111/j.1749-6632.1988.tb18788.x. [DOI] [PubMed] [Google Scholar]
  4. England P. J. Intracellular calcium receptor mechanisms. Br Med Bull. 1986 Oct;42(4):375–383. doi: 10.1093/oxfordjournals.bmb.a072155. [DOI] [PubMed] [Google Scholar]
  5. Grubauer G., Elias P. M., Feingold K. R. Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res. 1989 Mar;30(3):323–333. [PubMed] [Google Scholar]
  6. Grubauer G., Feingold K. R., Elias P. M. Relationship of epidermal lipogenesis to cutaneous barrier function. J Lipid Res. 1987 Jun;28(6):746–752. [PubMed] [Google Scholar]
  7. Harris H. W., Grunfeld C., Feingold K. R., Rapp J. H. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice. J Clin Invest. 1990 Sep;86(3):696–702. doi: 10.1172/JCI114765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hennings H., Holbrook K. A., Yuspa S. H. Factors influencing calcium-induced terminal differentiation in cultured mouse epidermal cells. J Cell Physiol. 1983 Sep;116(3):265–281. doi: 10.1002/jcp.1041160303. [DOI] [PubMed] [Google Scholar]
  9. Hennings H., Holbrook K. A., Yuspa S. H. Potassium mediation of calcium-induced terminal differentiation of epidermal cells in culture. J Invest Dermatol. 1983 Jul;81(1 Suppl):50–5s. doi: 10.1111/1523-1747.ep12540491. [DOI] [PubMed] [Google Scholar]
  10. Hennings H., Michael D., Cheng C., Steinert P., Holbrook K., Yuspa S. H. Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell. 1980 Jan;19(1):245–254. doi: 10.1016/0092-8674(80)90406-7. [DOI] [PubMed] [Google Scholar]
  11. Hennings H., Steinert P., Buxman M. M. Calcium induction of transglutaminase and the formation of epsilon(gamma-glutamyl) lysine cross-links in cultured mouse epidermal cells. Biochem Biophys Res Commun. 1981 Sep 30;102(2):739–745. doi: 10.1016/s0006-291x(81)80194-5. [DOI] [PubMed] [Google Scholar]
  12. Latorre R., Oberhauser A., Labarca P., Alvarez O. Varieties of calcium-activated potassium channels. Annu Rev Physiol. 1989;51:385–399. doi: 10.1146/annurev.ph.51.030189.002125. [DOI] [PubMed] [Google Scholar]
  13. Lo J. S., Oriba H. A., Maibach H. I., Bailin P. L. Transepidermal potassium ion, chloride ion, and water flux across delipidized and cellophane tape-stripped skin. Dermatologica. 1990;180(2):66–68. doi: 10.1159/000247992. [DOI] [PubMed] [Google Scholar]
  14. Menon G. K., Feingold K. R., Moser A. H., Brown B. E., Elias P. M. De novo sterologenesis in the skin. II. Regulation by cutaneous barrier requirements. J Lipid Res. 1985 Apr;26(4):418–427. [PubMed] [Google Scholar]
  15. Menon G. K., Grayson S., Elias P. M. Ionic calcium reservoirs in mammalian epidermis: ultrastructural localization by ion-capture cytochemistry. J Invest Dermatol. 1985 Jun;84(6):508–512. doi: 10.1111/1523-1747.ep12273485. [DOI] [PubMed] [Google Scholar]
  16. Proksch E., Elias P. M., Feingold K. R. Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements. J Clin Invest. 1990 Mar;85(3):874–882. doi: 10.1172/JCI114514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rodwell V. W., Nordstrom J. L., Mitschelen J. J. Regulation of HMG-CoA reductase. Adv Lipid Res. 1976;14:1–74. doi: 10.1016/b978-0-12-024914-5.50008-5. [DOI] [PubMed] [Google Scholar]
  18. Rubin R. P. The role of calcium in the release of neurotransmitter substances and hormones. Pharmacol Rev. 1970 Sep;22(3):389–428. [PubMed] [Google Scholar]
  19. Schoen R. E., Frishman W. H., Shamoon H. Hormonal and metabolic effects of calcium channel antagonists in man. Am J Med. 1988 Mar;84(3 Pt 1):492–504. doi: 10.1016/0002-9343(88)90272-0. [DOI] [PubMed] [Google Scholar]
  20. Siegenthaler U., Laine A., Polak L. Studies on contact sensitivity to chromium in the guinea pig. The role of valence in the formation of the antigenic determinant. J Invest Dermatol. 1983 Jan;80(1):44–47. doi: 10.1111/1523-1747.ep12531034. [DOI] [PubMed] [Google Scholar]
  21. Smith R. J., Iden S. S. Phorbol myristate acetate-induced release of granule enzymes from human neutrophils: inhibition by the calcium antagonist, 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride. Biochem Biophys Res Commun. 1979 Nov 14;91(1):263–271. doi: 10.1016/0006-291x(79)90612-0. [DOI] [PubMed] [Google Scholar]
  22. Stanley J. R., Yuspa S. H. Specific epidermal protein markers are modulated during calcium-induced terminal differentiation. J Cell Biol. 1983 Jun;96(6):1809–1814. doi: 10.1083/jcb.96.6.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Triggle D. J., Janis R. A. Calcium channel ligands. Annu Rev Pharmacol Toxicol. 1987;27:347–369. doi: 10.1146/annurev.pa.27.040187.002023. [DOI] [PubMed] [Google Scholar]
  24. Villereal M. L., Palfrey H. C. Intracellular calcium and cell function. Annu Rev Nutr. 1989;9:347–376. doi: 10.1146/annurev.nu.09.070189.002023. [DOI] [PubMed] [Google Scholar]
  25. Yuspa S. H., Kilkenny A. E., Steinert P. M., Roop D. R. Expression of murine epidermal differentiation markers is tightly regulated by restricted extracellular calcium concentrations in vitro. J Cell Biol. 1989 Sep;109(3):1207–1217. doi: 10.1083/jcb.109.3.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]

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