Inhibition of calcium-induced terminal differentiation of epidermal cells by ouabain and A23187.

Mouse epidermal basal cells can be selectively grown in a medium containing 0.02-0.1 mM Ca++. Terminal differentiation with squame formation and cell death is induced by elevating extracellular Ca++ to greater than 0.1mM. A variety of agents were studied as modifiers of this calcium-induced terminal differentiation. Other than Ca++, no inorganic cation tested was active in inducing or preventing differentiation. Organic cations, local anesthetics, quercetin, and the ionophore X 537A were also without effect. Limited non-toxic exposures to macromolecular synthesis inhibitors or microtubule and microfilament disruptors, and prolonged exposure to indomethacin or protease inhibitors did not alter differentiation. The skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate markedly accelerated calcium-induced epidermal differentiation while the ionophore A23187 and the Na+-K+ATPase inhibitor ouabain (at non-toxic concentrations) clearly inhibited the induction by calcium. These results suggest that epidermal differentiation is specifically triggered by elevation of extracellular calcium but may be mediated by the flux or intracellular levels of other ions, particularly Na+ or K+.