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oai:uvadoc.uva.es:10324/59522024-12-16T12:06:39Zcom_10324_1133com_10324_931com_10324_894col_10324_1209

Hernández San Miguel, Esther Vay, Laura Santo Domingo Mayoral, Jaime Domínguez Lobatón, María Carmen Moreno Díaz-Calderón, Alfredo Montero Zoccola, María Teresa Álvarez Martín, Javier 2014-09-15T12:01:52Z 2014-09-15T12:01:52Z 2006 Cell Calcium, 2006, vol. 40, p. 53-61 0143-4160 http://uvadoc.uva.es/handle/10324/5952 10.1016/j.ceca.2006.03.009 53 61 Cell Calcium 40 Producción Científica There is increasing evidence that mitochondria play an important role in the control of cytosolic Ca2+ signaling. We show here that the main mitochondrial Ca2+-exit pathway, the mitochondrial Na+/Ca2+ exchanger, controls the pattern of cytosolic Ca2+ oscillations in nonexcitable cells. In HeLa cells, the inhibitor of the mitochondrial Na+/Ca2+ exchanger CGP37157 changed the pattern of the oscillations induced by histamine from a high-frequency irregular one to a lower frequency baseline spike type, surprisingly with little changes in the average Ca2+ values of a large cell population. In human fibroblasts, CGP37157 increased the frequency of the baseline oscillations in cells having 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 activated histamine-induced Ca2+ release from the endoplasmic reticulum and increased the size of the cytosolic Ca2+ peak induced by histamine in 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. application/pdf eng Elsevier Ltd. info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ Attribution-NonCommercial-NoDerivatives 4.0 International Calcio - Metabolismo The mitochondrial Na+/Ca2+ exchanger plays a key role in the control of cytosolic Ca2+ oscillations info:eu-repo/semantics/article SI