CaMKII regulates intracellular calcium stores of native endothelial cells from mesenteric arteries

Abstract

Ca2+ homeostasis is crucial for endothelial function and the regulation of vascular tone. The Ca2+‐dependent kinase CaMKII is activated by Ca2+ pulsars and might play an important role in endothelial Ca2+ homeostasis. Thus, the involvement of endothelial CaMKII in the regulation of intracellular Ca2+ dynamics has been investigated in native endothelial cells of mesenteric arteries. Acute exposure to KN‐93 (10 μM), a CaMKII inhibitor, has little if any effect on Ca2+ pulsars frequency or amplitude. However, CaMKII inhibition induces pulsar sites recruitment as more pulsars sites are active in the presence of KN‐93 compared to control (25%). Interestingly, in absence of extracellular Ca2+, KN‐93 appears to empty intracellular Ca2+ stores. Indeed, exposure to ionomycin, to empty endoplasmic reticulum in absence of extrallular Ca2+, provoked a large and transient intracellular Ca2+ increase. However, preincubation with KN‐93 abolished the ionomycin‐induced Ca2+ transient. These results suggest that CaMKII might inhibit IP3R receptors and/or phosphorylates phospholamban to regulate ER Ca2+ content. Confocal microscopy revealed that CaMKIIα & β are colocalized with IP3R1 in native endothelium. Our data suggest that CaMKII is an important regulator of endothelial Ca2+ homeostasis and may represent a novel target for the treatment of pathologies like hypertension.Supported by FRSQ, CFI, CIHR and HSFC.