Orai1 calcium channels in the vasculature

Orai1 was discovered in T cells as a calcium-selective channel that is activated by store depletion. Recent studies suggest that it is expressed and functionally important also in blood vessels, not only because haematopoietic cells can incorporate in the vascular wall but also because Orai1 is expressed and functional in vascular smooth muscle cells and endothelial cells. This article summarises the arising observations in this new area of vascular research and debates underlying issues and challenges for future investigations. The primary focus is on vascular smooth muscle cells and endothelial cells. Specific topics include Orai1 expression; Orai1 roles in store-operated calcium entry and ionic currents of store-depleted cells; blockade of Orai1-related signals by Synta 66 and other pharmacology; activation or regulation of Orai1-related signals by physiological substances and compartments; stromal interaction molecules and the relationship of Orai1 to other ion channels, transporters and pumps; transient receptor potential canonical channels and their contribution to store-operated calcium entry; roles of Orai1 in vascular tone, remodelling, thrombus formation and inflammation; and Orai2 and Orai3. Overall, the observations suggest the existence of an additional, previously unrecognised, calcium channel of the vascular wall that is functionally important particularly in remodelling but probably also in certain vasoconstrictor contexts.