Figure 1.
An evidence-based or potential association between epidermal calcium gradients and the epidermal barrier. Epidermal calcium gradients have been altered in keratitis-ichthyosis-deafness (KID) syndrome induced by gap junction protein beta 2 (GJB2) or GJB6 missense mutations and in chronological skin aging. The formation and homeostasis of the epidermal calcium gradients could be regulated by the calcium-sensing receptor (CaR), transient receptor potential (TRP) channels, and store-operated calcium entry (SOCE) channels. CaR deletion, which inhibits Ca2+ influx, impairs the epidermal barrier in mice. In TRP channels, TRP vanilloid 4 (TRPV4) activation, which could be induced by heat (>30 °C) and hypo-osmolarity, plays an important role in epidermal barrier formation and recovery in mice. On the other hand, the blockade of TRPV1 activation by physical and chemical stimuli such as heat (42 °C) and capsaicin can suppress atopic dermatitis (AD)-like symptoms in mice. Two essential components of SOCE, STIM1 (stromal interaction molecule1) and Orai1 (ORAI calcium release-activated calcium modulator 1), are activated by endoplasmic reticulum (ER) calcium store depletion. Downregulation of Orai1 can impair keratinocyte differentiation and barrier homeostasis in mice.