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 22-nov-2024