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Title

Mitochondrial regulation of sarcoplasmic reticulum Ca2+ content in vascular smooth muscle cells

Authors
Liao, Chiu-Hsiang
van Breemen, Cornelis
Published in Circulation Research. 2009, vol. 104, no. 1, p. 104-12
Abstract Subplasmalemmal ion fluxes have global effects on Ca(2+) signaling in vascular smooth muscle. Measuring cytoplasmic and mitochondrial [Ca(2+)]and [Na(+)], we previously showed that mitochondria buffer both subplasmalemmal cytosolic [Ca(2+)] and [Na(+)] in vascular smooth muscle cells. We have now directly measured sarcoplasmic reticulum [Ca(2+)] in aortic smooth muscle cells, revealing that mitochondrial Na(+)/Ca(2+) exchanger inhibition with CGP-37157 impairs sarcoplasmic reticulum Ca(2+) refilling during purinergic stimulation. By overexpressing hFis1 to remove mitochondria from the subplasmalemmal space, we show that the rate and extent of sarcoplasmic reticulum refilling is augmented by a subpopulation of peripheral mitochondria. In ATP-stimulated cells, hFis-1-mediated relocalization of mitochondria impaired the sarcoplasmic reticulum refilling process and reduced mitochondrial [Ca(2+)] elevations, despite increased cytosolic [Ca(2+)] elevations. Reversal of plasmalemmal Na(+)/Ca(2+) exchange was the primary Ca(2+) entry mechanism following ATP stimulation, based on the effects of KB-R7943. We propose that subplasmalemmal mitochondria ensure efficient sarcoplasmic reticulum refilling by cooperating with the plasmalemmal Na(+)/Ca(2+) exchanger to funnel Ca(2+) into the sarcoplasmic reticulum and minimize cytosolic [Ca(2+)] elevations that might otherwise contribute to hypertensive or proliferative vasculopathies.
Keywords Adenosine Triphosphate/pharmacologyAnimalsAortaCalcium/metabolismCalcium Signaling/drug effects/physiologyCell CompartmentationCell Membrane/metabolismClonazepam/analogs & derivatives/pharmacologyHypertension/pathologyMembrane Proteins/genetics/physiologyMitochondria, Muscle/physiologyMitochondrial Proteins/genetics/physiologyMuscle, Smooth, Vascular/cytologyMyocytes, Smooth Muscle/metabolism/ultrastructureRatsRecombinant Fusion Proteins/physiologySarcoplasmic Reticulum/metabolismSodium/metabolismSodium-Calcium Exchanger/drug effects/metabolismThiazepines/pharmacologyThiourea/analogs & derivatives/pharmacology
Stable URL http://archive-ouverte.unige.ch/unige:1274
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Identifiers
PMID: 19023135
Structures
Research group Signaux intracellulaires (210)

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Deposited on : 2009-03-31

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