Heterogeneous Cytoplasmic Calcium Response in Microvascular Endothelial Cells

We investigated changes in calcium concentration in response to the administration of ATP and the onset of shear stress with cultured rat adrenomedulary endothelial cells (RAMECs, microvascular). A substantial heterogeneity in time and space in the calcium response was observed. The onset of shear stress induced calcium waves that originated from one or several cells and propagated to neighboring cells. The application of uniform exogenous ATP produced similar heterogeneous calcium transients. The size of the responding groups was dependent on ATP concentration. The propagation of calcium waves induced by either ATP or shear stress challenge was significantly suppressed by suramin, a non-specific purinergic receptor blocker. We investigated some of the mechanisms leading to the heterogeneity, and the results indicated that the main source of variation is the heterogeneous distribution of purinergic receptor. The application of ATP or shear stress stimulates cells to release ATP causing an increase of [Ca²⁺ ]_i via purinergic receptor in the cells that have high sensitivity. Subsequently, additional ATP is released and the elevation of ATP concentration in the vicinity of the initially responding cells mediates the calcium propagation. These data suggest a mechanism by which ATP acts as an autocrine and paracrine mediator to integrate individual cell responses that result in coordination of vascular functions in situ