Intercellular Ca²⁺ Response Triggered by IP₃ among Endothelial Cells in Shear Stress Flow

Abstract

A phenomenon has been observed in which intracellular Ca²⁺ concentration in endothelial cells increases upon application of shear stress (Ca²⁺ response). It is therefore assumed that Ca²⁺ is the second messenger in the transfer of shear stress stimulation into cells. The Ca²⁺ response is also known to spread to surrounding cells (Ca²⁺ wave). We investigated the effects on Ca²⁺ wave among cultured bovine aorta endothelial cells (BAECs) upon inhibiting the main intercellular signaling pathways, such as gap junction and paracrine pathways by inducing Ca²⁺ wave using D-myo-inositol 1,4,5-trisphosphate, P4(5)-(1-(2-nitrophenyl)ethyl) ester trisodium salt (Caged IP₃) due to an intracellular IP₃ elevation. In addition, we investigated the Ca²⁺ wave among BAECs under shear stress loading. Using Caged IP₃, local release of ATP from BAEC induced Ca²⁺ wave. The Ca²⁺ wave was inhibited by the inhibitors of paracrine pathways. Furthermore, the Ca²⁺ response spread in the direction of the downstream under shear flow. These results suggest that paracrine pathway is dominant in both of flow and no flow conditions.