Selective obliteration of the epidermal calcium gradient leads to enhanced lamellar body secretion

The epidermal permeability barrier is formed by lipids delivered to the intercellular spaces through the secretion of lamellar bodies. Prior studies have shown that the rate of lamellar body secretion appears to be regulated by the extracellular calcium content of the upper epidermis, which is altered following permeability barrier disruption. To determine 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 physiologic Ca++ (and K+) versus ion-free solutions across hairless mouse stratum corneum. Sonophoresis at 15 MHz did not alter barrier function, but in the absence of Ca++ the extracellular calcium content of the outer epidermis, as revealed by ion capture cytochemistry, was displaced downward toward the basal layer and dermis. In contrast, following sonophoresis of Ca(++)-containing solutions, the extracellular Ca++ gradient became obscured by excess Ca++ in the cytosol at all levels of the epidermis. These changes in the extracellular calcium content lead, in turn, to accelerated lamellar body secretion (with low Ca++), or basal rates of lamellar body secretion (with normal Ca++). These results demonstrate that the epidermal extracellular calcium content in the upper epidermis can be manipulated by sonophoresis without prior barrier disruption, and that changes in the Ca++ gradient induce lamellar body secretion, independent of barrier disruption.