RT info:eu-repo/semantics/article T1 The mitochondrial Na+/Ca2+ exchanger plays a key role in the control of cytosolic Ca2+ oscillations A1 Hernández San Miguel, Esther A1 Vay, Laura A1 Santo Domingo, Jaime A1 Domínguez Lobatón, María Carmen A1 Moreno Díaz-Calderón, Alfredo A1 Montero Zoccola, María Teresa A1 Álvarez Martín, Javier K1 Calcio - Metabolismo AB There is increasing evidence that mitochondria play an important role in the control of cytosolic Ca2+ signaling. We show here that themain mitochondrial Ca2+-exit pathway, the mitochondrial Na+/Ca2+ exchanger, controls the pattern of cytosolic Ca2+ oscillations in nonexcitablecells. In HeLa cells, the inhibitor of the mitochondrial Na+/Ca2+ exchanger CGP37157 changed the pattern of the oscillationsinduced by histamine from a high-frequency irregular one to a lower frequency baseline spike type, surprisingly with little changes in theaverage Ca2+ values of a large cell population. In human fibroblasts, CGP37157 increased the frequency of the baseline oscillations in cellshaving spontaneous activity and induced the generation of oscillations in cells without spontaneous activity. This effect was dose-dependent,disappeared when the inhibitor was washed out and was not mimicked by mitochondrial depolarization. CGP37157 increased mitochondrial[Ca2+] and ATP production in histamine-stimulated HeLa cells, but the effect on ATP production was only transient. CGP37157 also activatedhistamine-induced Ca2+ release from the endoplasmic reticulum and increased the size of the cytosolic Ca2+ peak induced by histaminein HeLa cells. Our results suggest that the mitochondrial Na+/Ca2+ exchanger directly modulates inositol 1,4,5-trisphosphate-induced Ca2+release and in that way controls cytosolic Ca2+ oscillations. PB Elsevier Ltd. SN 0143-4160 YR 2006 FD 2006 LK http://uvadoc.uva.es/handle/10324/5952 UL http://uvadoc.uva.es/handle/10324/5952 LA eng NO Cell Calcium, 2006, vol. 40, p. 53-61 NO Producción Científica DS UVaDOC RD 30-abr-2024