Characterization of Store-Operated Calcium Channels in Pancreatic Duct Epithelia

Abstract

Store-operated Ca2+ channels (SOCs) are activated by depletion of intracellular Ca2+ stores following agonist-mediated Ca2+ release. In pancreatic duct epithelial cells (PDEC), the activation of GPCR coupled to phospholipase C stimulated SOC-mediated Ca2+ influx. Direct measurement of [Ca2+] in the ER showed that SOCs slowed ER depletion. SOC-mediated currents were inwardly rectifying and greatly increased in the absence of divalent cations, as typical for SOCs in other cell types. Pharmacology of epithelial SOCs was consistent with that of some types of SOCs. In polarized PDEC, SOCs were localized specifically to the basolateral membrane. Both STIM and Orai proteins were expressed in PDEC and were colocalized after store depletion. Furthermore, knockdown of Orai3 expression, the most abundant Orai subtype, reduced SOC-mediated Ca2+ influx significantly. In conclusion, basolateral Ca2+ entry through SOCs fills internal Ca2+ stores depleted by external stimuli and facilitates Ca2+-dependent cellular processes such as salt and mucin secretion from the exocrine pancreatic ducts.