Figure 8. Model depicting the pathway stimulated by TNFα to increase venous endothelial permeability.

TNFα-R1 induces opening of Panx1 channels at the plasma membrane (through SRC) that release ATP from the cytosol to the extracellular environment. ATP is hydrolyzed by CD39 and CD73 to adenosine which then stimulates A_2A/A_2B receptors. TRPV4 channel are activated, resulting in an increase in paracellular leak through venous tight junction remodeling.