Sanz-Lázaro, SaraJimenez-Pompa, AmandaHernández-Vivanco, AliciaCarmona-Hidalgo, BeatrizGarcía-Magro, NuriaGarcía-Magro, NuriaPerez-Alvarez, AlbertoCaba-González, Jose CarlosRueda-Ruzafa, LolaAlbillos, Almudena2026-01-272026-01-272025-12Sanz-Lázaro, S, Jimenez-Pompa, A, Hernández-Vivanco, A, Carmona-Hidalgo, B, García-Magro, N, Perez-Alvarez, A, Caba-González, J C, Rueda-Ruzafa, L & Albillos, A 2025, 'The release of catecholamines to the cytosol and the exocytosis of secretory vesicles triggered by IP 3 in chromaffin cells', American Journal of Physiology - Cell Physiology, vol. 329, no. 6, pp. C2022-C2035. https://doi.org/10.1152/ajpcell.00328.20250363-6143https://hdl.handle.net/10641/7596Publisher Copyright: Copyright © 2025 The Authors.The aim of the present study was to investigate the secretory responses elicited by inositol 1,4,5-trisphosphate (IP3) and their regulation by Ca2 + from different sources. Fura-2, carbon fiber amperometry, and plasma membrane capacitance recordings were performed in mouse chromaffin cells to evaluate cytosolic Ca2 + changes, catecholamine release, and exocytosis, respectively. Amperometric recordings revealed that IP3 triggered the continuous release of catecholamines to the cytosol with a plateau shape, either applied independently or in combination with the V-ATPase blocker bafilomycin A1, without exhibiting additive effects, which suggests that V-ATPase blockade might be a potential mechanism of action. The catecholamine release elicited by IP3 can take place in the absence of cytosolic Ca2 + ; however, it may be also regulated by it through a bell-shaped mechanism, with the contribution of Ca2 + stored in intracellular organelles. Furthermore, plasma membrane capacitance recordings showed that IP3 could also elicit exocytosis of secretory vesicles with the participation of intracellular organelle Ca2 + stores. This exocytosis could be regulated by vesicular or cytosolic Ca2 + , as shown in experiments with bafilomycin A1 or the Ca2 + chelator BAPTA-AM, respectively, and by kaempferol, an activator of the mitochondrial Ca2 + uniporter, suggesting that mitochondria may exert physiologically this Ca2 + regulatory mechanism. Therefore, in the IP3-mediated secretion, Ca2 + from different sources control the different steps of catecholamine release from the secretory vesicle to the cytosol and then finally to the extracellular space.4722248enghttp://creativecommons.org/licenses/by-nc-nd/4.0/IPamperometrycalciumcapacitancecatecholaminePhysiologyCell BiologyJournal ArticleYesyesjournal articleopen access10.1152/ajpcell.00328.2025https://www.scopus.com/pages/publications/105024249192https://www.scopus.com/pages/publications/105024249192#tab=citedBy