Calcium spots: elementary signals in response to mechanical stress in vascular endothelial cells.

Abstract

Blood flow–mediated mechanical force, ie, shear stress, plays an important role in regulation of vascular function and development of various cardiovascular diseases.1 2 3 It directly stimulates vascular endothelial cells to mobilize intracellular Ca2+ ([Ca2+]i), resulting in production of endothelium-derived vasoactive substances, such as nitric oxide and prostacyclin, which cause vasodilation by acting on smooth muscle cells.1 2 3 In this process, the mechanosensitive (MS) channel is an important pathway mediating the shear stress–induced increase in [Ca2+]i.4 5 6 7 In addition, a specific vasoactive agonist, ATP, has been regarded as an important shear transducer of the endothelial [Ca2+]i mobilization in response to fluid flow.8 9 10 11 Which initiates and mainly contributes to the [Ca2+]i mobilization, MS channel or the shear transducer? The mechanism underlying the flow-induced [Ca2+]i mobilization is controversial. Furthermore, little is known about the spatiotemporal properties of [Ca2+]i mobilization triggered by MS channels or by the shear transducers. In this issue of Circulation Research , Ohata et al12 demonstrate novel spatiotemporal changes in [Ca2+]i in response to fluid flow in cultured bovine aortic endothelial cells under the application of lysophosphatidic acid (LPA),13 14 a bioactive phospholipid. Using real-time confocal microscopy equipped with a multipinhole Nipkow disk–type scanner, it was shown that superfusion of the cells with LPA at physiologically relevant concentrations and flow rates produced spot-like elevations of [Ca2+]i, ie, Ca2+ spots, which were localized to a circular area (<4 μm diameter), followed by gradual and concentric spread throughout the cells. The Ca2+ spots develop sporadically but exhibit a distinct spatiotemporal pattern from Ca2+ sparks, the elementary [Ca2+] …