Distinct Ca2+-permeable cation currents are activated by internal Ca2+-store depletion in RBL-2H3 cells and human salivary gland cells, HSG and HSY

Store-operated Ca2+ influx, suggested to be mediated via store-operated cation channel (SOC), is present in all cells. The molecular basis of SOC, and possible heterogeneity of these channels, are still a matter of controversy. Here we have compared the properties of SOC currents (I-SOC) in human sub-mandibular glands cells (HSG) and human parotid gland cells (HSY) with I-CRAC (Ca2+ release-activated Ca2+ current) in RBL cells. Internal Ca2+ store-depletion with IP3 or thapsigargin activated cation channels in all three cell types. 1 muM Gd3+ blocked channel activity in all cells. Washout of Gd3+ induced partial recovery in HSY and HSG but not RBL cells. 2-APB reversibly inhibited the channels in all cells. in RBL cells displayed strong inward rectification with E-rev(Ca) = > + 90 mV and E-rev (Na) = +60 mV. I-SOC in HSG cells showed weaker rectification with E-rev(Ca) = +25 mV and L-rev (Na) + 10 mV. HSY cells displayed a linear current with E-rev = + 5 mV, which was similar in Ca2+_ or Na+-containing medium. pCa/pNa was > 500, 40, and 4.6 while pCs /pNa was 0. 1, 1, and 1. 3, for RBL, HSG, and HSY cells, respectively. Evidence for anomalous mole fraction behavior of Ca2+ /Na+ permeation was obtained with RBL and HSG cells but not HSY cells. Additionally, channel inactivation with Ca (2+) + Na+ or Na+ in the bath was different in the three cell types. In aggregate, these data demonstrate that distinct store-dependent cation currents are stimulated in RBL, HSG, and HSY cells. Importantly, these data suggest a molecular heterogeneity, and possibly cell-specific differences in the function, of these channels.