Fig. 6. Pathways for Ca²⁺ signaling in normal and DD keratinocytes. Raised extracellular Ca²⁺ binds to a Ca²⁺ receptor (CaR), located in the plasma membrane, producing the second messenger inositol-1,4,5-trisphosphate (IP3). IP3 causes Ca²⁺ release from the endoplasmic reticulum (ER) and the Golgi by binding to IP3 receptors (IP3R). Emptying of intracellular Ca²⁺ stores activates Ca²⁺ influx through several pathways, including capacitive Ca²⁺ influx and influx through a Ca²⁺-permeable, Ca²⁺-activated non-selective cation channel (NSCC). In this drawing, calcium fluxes are denoted by solid arrows. Thick and thin arrows represent relative increases and decreases, respectively, in calcium flux between normal and DD keratinocytes: Ca²⁺ release from the ER decreases, whereas Ca²⁺ release from the Golgi and capacitive Ca²⁺ influx increase in DD cells relative to normal cells.