Abstract
Store-operated Ca(2+) entry (SOCE) is a conserved mechanism of Ca(2+) influx that regulates Ca(2+) signaling in many cell types. SOCE is activated by depletion of endoplasmic reticulum (ER) Ca(2+) 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 Ca(2+)-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 Ca(2+)-activated chloride channel TMEM16A is inactive and fails to secrete Cl(-), resulting in anhidrosis in mice and human patients.