SELECTIVE OBLITERATION OF THE EPIDERMAL CALCIUM GRADIENT LEADS TO ENHANCED LAMELLAR BODY SECRETION

The epidermal permeability barrier is formed by lipids delivered to th e intercellular spaces through the secretion of lamellar bodies. Prior studies have shown that the rate of lamellar body secretion appears t o be regulated by the extracellular calcium content of the upper epide rmis, which is altered following permeability barrier disruption. To d etermine directly whether changes in extracellular calcium content in the upper epidermis versus disruption of the barrier regulate lamellar body secretion, we experimentally manipulated the Ca++ content of the upper epidermis by sonophoresis of aqueous solutions containing physi ologic Ca++ (and K+) versus ion-free solutions across hairless mouse s tratum corneum. Sonophoresis at 15 MHz did not alter barrier function, but in the absence of Ca++ the extracellular calcium content of the o uter epidermis, as revealed by ion capture cytochemistry, was displace d downward toward the basal layer and dermis. In contrast, following s onophoresis of Ca++-containing solutions, the extracellular Ca++ gradi ent became obscured by excess Ca++ in the cytosol at all levels of the epidermis. These changes in the extracellular calcium content lead, i n turn, to accelerated lamellar body secretion (with low Ca++), or bas al rates of lamellar body secretion (with normal Ca++). These results demonstrate that the epidermal extracellular calcium content in the up per epidermis can be manipulated by sonophoresis without prior barrier disruption, and that changes in the Ca++ gradient induce lamellar bod y secretion, independent of barrier disruption.