en
Scientific article
English

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

Published inCirculation research, vol. 104, no. 1, p. 104-112
Publication date2009
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/pharmacology
  • Animals
  • Aorta
  • Calcium/metabolism
  • Calcium Signaling/drug effects/physiology
  • Cell Compartmentation
  • Cell Membrane/metabolism
  • Clonazepam/analogs & derivatives/pharmacology
  • Hypertension/pathology
  • Membrane Proteins/genetics/physiology
  • Mitochondria, Muscle/physiology
  • Mitochondrial Proteins/genetics/physiology
  • Muscle, Smooth, Vascular/cytology
  • Myocytes, Smooth Muscle/metabolism/ultrastructure
  • Rats
  • Recombinant Fusion Proteins/physiology
  • Sarcoplasmic Reticulum/metabolism
  • Sodium/metabolism
  • Sodium-Calcium Exchanger/drug effects/metabolism
  • Thiazepines/pharmacology
  • Thiourea/analogs & derivatives/pharmacology
Citation (ISO format)
POBURKO, Damon et al. Mitochondrial regulation of sarcoplasmic reticulum Ca2+ content in vascular smooth muscle cells. In: Circulation research, 2009, vol. 104, n° 1, p. 104–112. doi: 10.1161/CIRCRESAHA.108.180612
Main files (1)
Article (Accepted version)
accessLevelRestricted
Identifiers
ISSN of the journal0009-7330
533views
0downloads

Technical informations

Creation03/31/2009 4:02:00 PM
First validation03/31/2009 4:02:00 PM
Update time03/14/2023 3:03:52 PM
Status update03/14/2023 3:03:52 PM
Last indexation01/15/2024 6:20:19 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack