Regulation of epithelial ion transport in exocrine glands by store-operated Ca2+ entry

Abstract

Store-operated Ca²⁺ entry (SOCE) is a conserved mechanism of Ca²⁺ influx that regulates Ca²⁺ signaling in many cell types. SOCE is activated by depletion of endoplasmic reticulum (ER) Ca²⁺ stores in response to physiological agonist stimulation. After it was first postulated by J.W. Putney Jr. in 1986, SOCE has been described in a large number of non-excitable cell types including secretory cells of different exocrine glands. Here we discuss the mechanisms by which SOCE controls salt and fluid secretion in exocrine glands, with a special focus on eccrine sweat glands. In sweat glands, SOCE plays an important, non-redundant role in regulating the function of Ca²⁺-activated Cl^- channels (CaCC), Cl^- secretion and sweat production. In the absence of key regulators of SOCE such as the CRAC channel pore subunit ORAI1 and its activator STIM1, the Ca²⁺-activated chloride channel TMEM16A is inactive and fails to secrete Cl^-, resulting in anhidrosis in mice and human patients.

Keywords: CaCC; Fluid secretion; ORAI1; STIM1; Sweat glands; TMEM16A.