title: Store-operated calcium entry compensates fast ER calcium loss in resting hippocampal neurons.
abstract: The endoplasmic reticulum (ER) acts as a dynamic calcium store and is involved in the generation of specific patterns of calcium signals in neurons. Calcium is mobilized from the ER store by multiple signaling cascades, and neuronal activity is known to regulate ER calcium levels. We asked how neurons regulate ER calcium levels in the resting state. Direct ER calcium imaging showed that ER calcium was lost quite rapidly from the somatic and dendritic ER when resting neurons were transiently kept under calcium-free conditions. Interestingly, free ER and free cytosolic calcium was lost continuously across the plasma membrane and was not held back in the cytosol, implying the presence of a prominent calcium influx mechanism to maintain ER calcium levels at rest. When neurons were treated acutely with inhibitors of store-operated calcium entry (SOCE), an immediate decline in ER calcium levels was observed. This continuous SOCE-like calcium entry did not require the activation of a signaling cascade, but was rather a steady-state phenomenon. The SOCE-like mechanism maintains medium-high ER calcium levels at rest and is essential for balanced resting calcium levels in the ER and cytosol.
authors.affiliation: Institute for Clinical Neurobiology, Julius-Maximilians-University of Würzburg, 97078 Würzburg, Germany. Electronic address: Samtleben_S@UKW.de.
authors.forename: Samira
authors.initials: S
authors.lastname: Samtleben
authors.affiliation: Institute for Clinical Neurobiology, Julius-Maximilians-University of Würzburg, 97078 Würzburg, Germany. Electronic address: Wachter_B@UKW.de.
authors.forename: Britta
authors.initials: B
authors.lastname: Wachter
authors.affiliation: Institute for Clinical Neurobiology, Julius-Maximilians-University of Würzburg, 97078 Würzburg, Germany. Electronic address: Blum_R@UKW.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Blum
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism*; D000071740:ORAI1 Protein; D000071741:ORAI2 Protein; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007093:Imidazoles; D008565:Membrane Proteins; D000071740:ORAI1 Protein; D000071741:ORAI2 Protein; C520430:Orai1 protein, mouse; C520431:Orai2 protein, mouse; C520432:Orai3 protein, mouse; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; C500145:Ces2c protein, mouse; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium
keywords: Calcium homeostasis; Calcium imaging; Calcium influx; Calcium store; Hippocampal neuron; Store-operated calcium entry