Grant: Operating Grant

Endothelial cells are cells lining the blood vessels and they play a crucial in the control of blood pressure and vascular tone. Mechanisms involved in the regulation of blood flow by the endothelium require intracellular Ca2+ ions as key signalling molecules. Our lab focuses on the investigation of the fundamental mechanisms controlling intracellular Ca2+ in endothelium. We have recently identified a unique and spontaneous Ca2+ signalling pathway in endothelium termed "Ca2+ pulsars". This novel Ca2+ signal has been shown to activate proteins at the cell membrane called ion channels and other proteins called kinases. Ca2+ pulsars are suggested to be involved in regulation of vascular function. However, the mechanisms underlying the regulation of this intracellular calcium signalling in the endothelium remain to be established. We seek to determine the relationship between Ca2+ pulsars and an important intracellular organelle, the mitochondria, which have been shown to regulate intracellular calcium. State-of-the-art confocal microscopy on living tissue and fluorescent probes will be used in conjunction with pharmacological approaches to assess the impact of mitochondria on Ca2+ pulsars and membrane potential of vascular cells, therefore on vascular function. Our work will provide novel insights on key mechanisms underlying the regulation of intracellular calcium signalling and its involvement in endothelial function and dysfunction. This research may provide crucial information regarding therapeutic targets for vascular disease such hypertension.