Mitochondria Modulates Calcium Pulsars In Native Endothelial Cells

Calcium (Ca2+) homeostasis is critical to endothelial function. Indeed, localized endothelial Ca2+ signals, such as Ca2+ pulsars - restricted IP3R-dependent Ca2+ releases within myoendothelial projection (MEP) - emerge as major modulators of vascular tone. However, Ca2+ pulsars regulation remains yet unexplored. Conversely, mitochondria appear to be an important regulator of intracellular Ca2+ signals in several cell types. We thus hypothesized that mitochondria regulates endothelial Ca2+ pulsar. Electron microscopy first showed an asymmetrical mitochondrial distribution in endothelium of mice mesenteric arteries, with a higher mitochondrial density near MEP. High-speed confocal microscopy was next used to study the impact of mitochondria on Ca2+ pulsars. Mitochondrial uncoupling by FCCP application unveiled pulsars active sites (+60%) but decreased discrete site frequency (-30%). Moreover, pharmacological alteration of mitochondrial Ca2+ import/export mechanisms (Kaempferol, Ru360, CGP37157) had a signif...