Dynamic properties of the tight junction barrier

A principal role of tight junctions is to seal the apical intercellular space and limit paracellular flux of ions and molecules. Despite the fact that tight junctions form heavily cross-linked structures, functional studies have fostered the hypothesis that the tight junction barrier is dynamic and defined by opening and closing events. However, it has been impossible to directly measure tight junction barrier function with sufficient resolution to detect such events. Nevertheless, recent electrophysiological and sieving studies have provided tremendous insight into the presence of at least two pathways of trans-tight junction flux: a high-capacity ion-selective “pore” pathway and a low-capacity “leak” pathway that allows the passage of macromolecules. Furthermore, it is now known that the tight junction molecular structure is highly dynamic and that dynamics are correlated with barrier function. Taken together, these data support a dynamic model of tight junction conductance and suggest that regulation of tight junction openings and closings may provide sensitive means of barrier regulation.