title: 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.
abstract: 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.
authors.affiliation: Laboratoire Canaux Calciques Fonctions et Pathologies, Inserm U607, DRDC/CEA, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France. abouron@cea.fr
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bouron
authors.forename: Xavier
authors.initials: X
authors.lastname: Altafaj
authors.forename: Sylvie
authors.initials: S
authors.lastname: Boisseau
authors.forename: Michel
authors.initials: M
authors.lastname: De Waard
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D019284:Thapsigargin; D007811:Lanthanum; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium