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.