Chronic exposure to stress hormones alters the subtype of store‐operated channels expressed in H19‐7 hippocampal neuronal cells

Differentiating H19‐7 hippocampal precursor cells up‐regulate (∼4.3‐fold) store‐operated channel (SOC) activity; relatively linear current‐voltage curves indicate an I SOC subtype of SOC. In differentiated H19‐7 neurons, the majority of agonist (arginine vasopressin, AVP)‐stimulated Ca 2+ entry occurs via SOCs, based on 2‐aminoethyldiphenylborinate (2‐APB) inhibition data and the observation that transient receptor potential C1 (TRPC1) channel knock down cells show a dramatic reduction of thapsigargin‐stimulated store‐operated Ca 2+ entry (SOCE) and inhibition of AVP‐stimulated Ca 2+ entry. Treatment of H19‐7 cells with the rat stress hormone corticosterone during differentiation induces a significant increase in AVP‐stimulated Ca 2+ entry, which is virtually eliminated by 2‐APB, suggesting a corticosterone‐induced increase of SOCE. Corticosterone also enhances AVP‐stimulated Mn 2+ entry, confirming an elevated Ca 2+ entry pathway, rather than a decreased Ca 2+ extrusion. When corticosterone addition is delayed until after H19‐7 cells have fully differentiated, it still elevates SOCE. In corticosterone‐treated H19‐7 cells, the knock down of TRPC1 no longer blocks thapsigargin‐stimulated Ca 2+ entry suggesting that the subtype of SOCs expressed in H19‐7 cells is altered by corticosterone treatment. Electrophysiological studies demonstrate that store‐operated currents in corticosterone‐treated H19‐7 cells exhibit a highly inward rectifying current‐voltage curve consistent with an I CRAC subtype of SOCs. Consistent with this finding is the observation that corticosterone treatment of H19‐7 cells increases the expression of the I CRAC channel subunit Orai1. Thus, the subtype of SOCs expressed in H19‐7 hippocampal neurons can be altered from I SOC to I CRAC by chronic treatment with stress hormones. J. Cell. Physiol. 228: 1332–1343, 2013. © 2012 Wiley Periodicals, Inc.