Effect of spatial heterogeneity and colocalization of eNOS and capacitative calcium entry channels on shear stress-induced NO production by endothelial cells: A modeling approach.

Introduction: Colocalization of endothelial nitric oxide synthase (eNOS) and capacitative Ca entry (CCE) channels in microdomains such as cavaeolae in endothelial cells (ECs) has been shown to significantly affect intracellular Ca dynamics and NO production, but the effect has not been well quantified.

Methods: We developed a two-dimensional continuum model of an EC integrating shear stress-mediated ATP production, intracellular Ca mobilization, and eNOS activation to investigate the effects of spatial colocalization of plasma membrane eNOS and CCE channels on Ca dynamics and NO production in response to flow-induced shear stress. Our model examines the hypothesis that subcellular colocalization of cellular components can be critical for optimal coupling of NO production to blood flow.