Integrity of the permeability barrier is crucial for maintenance of the epidermal calcium gradient.

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.