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Modulation of Ca2+ release and Ca2+ oscillations in HeLa cells and fibroblasts by mitochondrial Ca2+ uniporter stimulation

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dc.creator Vay, Laura
dc.creator Hernández-SanMiguel, Esther
dc.creator Santo-Domingo, Jaime
dc.creator Lobatón, Carmen D.
dc.creator Moreno, Alfredo
dc.creator Montero, Mayte
dc.creator Álvarez, Javier
dc.date 2008-06-20T07:38:09Z
dc.date 2008-06-20T07:38:09Z
dc.date 2007-04-01
dc.date.accessioned 2017-01-31T01:44:28Z
dc.date.available 2017-01-31T01:44:28Z
dc.identifier J Physiol. 2007 April 1; 580(Pt 1): 39–49
dc.identifier 0022-3751
dc.identifier http://hdl.handle.net/10261/5199
dc.identifier 10.1113/jphysiol.2006.126391
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5199
dc.description Copyright © by Blackwell Publishing Ltd.-- The definitive version is available at www.blackwell-synergy.com
dc.description The recent availability of activators of the mitochondrial Ca2+ uniporter allows direct testing of the influence of mitochondrial Ca2+ uptake on the overall Ca2+ homeostasis of the cell. We show here that activation of mitochondrial Ca2+ uptake by 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) or kaempferol stimulates histamine-induced Ca2+ release from the endoplasmic reticulum (ER) and that this effect is enhanced if the mitochondrial Na+–Ca2+ exchanger is simultaneously inhibited with CGP37157. This suggests that both Ca2+ uptake and release from mitochondria control the ability of local Ca2+ microdomains to produce feedback inhibition of inositol 1,4,5-trisphosphate receptors (InsP3Rs). In addition, the ability of mitochondria to control Ca2+ release from the ER allows them to modulate cytosolic Ca2+ oscillations. In histamine stimulated HeLa cells and human fibroblasts, both PPT and kaempferol initially stimulated and later inhibited oscillations, although kaempferol usually induced a more prolonged period of stimulation. Both compounds were also able to induce the generation of Ca2+ oscillations in previously silent fibroblasts. Our data suggest that cytosolic Ca2+ oscillations are exquisitely sensitive to the rates of mitochondrial Ca2+ uptake and release, which precisely control the size of the local Ca2+ microdomains around InsP3Rs and thus the ability to produce feedback activation or inhibition of Ca2+ release.
dc.description This work was supported by grants from Ministerio de Educación y Ciencia (BFU2005-05464), from Junta de Castilla y León (VA016A05) and from Fondo de Investigaciones Sanitarias (PI040789). J.S. and E.H.-S. hold research personnel training (FPI) and University personnel training (FPU) fellowships, respectively, from the Spanish Ministerio de Educación y Ciencia. L.V. holds a fellowship from Fondo de Investigaciones Sanitarias (Spanish Ministerio de Sanidad).
dc.description Peer reviewed
dc.format 22195 bytes
dc.format application/pdf
dc.language eng
dc.publisher Blackwell Publishing
dc.rights openAccess
dc.title Modulation of Ca2+ release and Ca2+ oscillations in HeLa cells and fibroblasts by mitochondrial Ca2+ uniporter stimulation
dc.type Artículo

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