Mitochondria Modulates Calcium Pulsars In Native Endothelial Cells

Calcium (Ca 2+ ) homeostasis is critical to endothelial function. Indeed, localized endothelial Ca 2+ signals, such as Ca 2+ pulsars ‐ restricted IP 3 R‐dependent Ca 2+ releases within myoendothelial projection (MEP) ‐ emerge as major modulators of vascular tone. However, Ca 2+ pulsars regulation remains yet unexplored. Conversely, mitochondria appear to be an important regulator of intracellular Ca 2+ signals in several cell types. We thus hypothesized that mitochondria regulates endothelial Ca 2+ 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 Ca 2+ pulsars. Mitochondrial uncoupling by FCCP application unveiled pulsars active sites (+60%) but decreased discrete site frequency (‐30%). Moreover, pharmacological alteration of mitochondrial Ca 2+ import/export mechanisms (Kaempferol, Ru360, CGP37157) had a significant impact on Ca 2+ pulsar dynamics. In summary, near‐MEP mitochondria might be an important modulator of Ca 2+ pulsars and hence of endothelial function. Support: FRQS, HSFC, CFI, SQHA and CIHR.