A store-operated Ca2+ influx activated in response to the depletion of thapsigargin-sensitive Ca2+ stores is developmentally regulated in embryonic cortical neurons from mice

Store-operated channels (SOCs) are recruited in response to the release of Ca2+ from intracellular stores. They allow a voltage-independent entry of Ca2+ into the cytoplasm also termed capacitative Ca2+ entry (CCE). In neurons, the functional significance of this Ca2+ route remains elusive. Several reports indicate that SOCs could be developmentally regulated. We verified the presence of a CCE in freshly dissociated cortical cells from E13, E14, E16, E18 fetuses and from 1-day-old mice. Intracellular Ca2+ stores were depleted by means of the SERCA pump inhibitor thapsigargin. At E13, the release of Ca2+ from thapsigargin-sensitive compartments gave rise to an entry of Ca2+ in a minority of cells. This Ca2+ route, insensitive to voltage-gated Ca2+ channel antagonists like Cd2+ and Ni2+, was blocked by the SOC inhibitor SKF-96365. After E13 and on E13 cells kept in culture, there is a marked increase in the percentage of cells with functional SOCs. The lanthanide La3+ fully inhibited the CCE from neonatal mice whereas it weakly blocked the thapsigargin-dependent Ca2+ entry at E13. This suggests that the subunit composition of the cortical SOCs is developmentally regulated with La3+-insensitive channels being expressed in the embryonic cortex whereas La3+-sensitive SOCs are found at birth. Our data argue for the presence of SOCs in embryonic cortical neurons. Their expression and pharmacological properties are developmentally regulated.