title: Integrity of the permeability barrier is crucial for maintenance of the epidermal calcium gradient.
abstract: Prior studies have demonstrated a Ca2+ gradient within the epidermis, with the highest concentration in the outer nucleated layers, disappearance of the Ca2+ gradient when the permeability barrier is acutely disrupted, and reappearance of the Ca2+ gradient in parallel with barrier repair, and disruption of the gradient in psoriasis. These observations suggest that integrity of the permeability barrier may maintain the epidermal Ca2+ gradient. To determine further whether a functional barrier is crucial for maintaining the Ca2+ gradient, we examined Ca2+ distribution by ion-capture cytochemistry in essential-fatty-acid-deficient (EFAD) and topical-lovastatin-treated mice, which display a chronic barrier abnormality. In both models, loss of the Ca2+ gradient occurred due to increased cytosolic Ca2+ in the lower epidermis, which normally displays a paucity of Ca2+. Moreover, artificial barrier restoration for 48 h with a water vapour-impermeable wrap normalized the Ca2+ distribution pattern. Acute barrier disruption also leads to the loss of the Ca2+ gradient, but in contrast with the chronic models, loss of the gradient was due to decreased Ca2+ in the upper epidermis. Occlusion with a vapour-impermeable wrap blocked restoration of the Ca2+ gradient after acute barrier disruption. These results demonstrate that chronic barrier disruption increases Ca2+ in the epidermis, and blockade of water flux normalizes Ca2+ distribution, whereas acute barrier disruption leads to loss of Ca2+, and blockade of water flux prevents the return of Ca2+. We conclude: (i) that the epidermal Ca2+ reservoir is derived from the movement of fluids and Ca2+ across the basement membrane, and (ii) that the integrity of the permeability barrier maintains the epidermal Ca2+ gradient.
authors.affiliation: Dermatology Service, Veterans Administration Medical Center, San Francisco, CA 94121.
authors.forename: G K
authors.initials: GK
authors.lastname: Menon
authors.forename: P M
authors.initials: PM
authors.lastname: Elias
authors.forename: K R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: D000096:Acetone / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004817:Epidermis / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D005228:Fatty Acids, Essential / Q000172:deficiency; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008854:Microscopy, Electron; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: D005228:Fatty Acids, Essential; D000096:Acetone; D008148:Lovastatin; D002118:Calcium