Student Presenter(s): Shivani Rana and Leyla Nasr
Faculty Mentor: Kurt Amsler
School/College: Osteopathic Medicine, Old Westbury

Confluent populations of MDCK II cells, a dog renal epithelial cell line, develop circumferential tight junctions joining adjacent cells to create a barrier to the paracellular movement of solutes and water. Previous work demonstrated that treatment of MDCK II and other epithelial cell types with a permeation enhancer, Na-caprate, increases paracellular permeability to both small ions (Pore Pathway) and large molecules (Leak Pathway) but the basis for this increase is not known. Focusing our studies on the less well-understood Leak Pathway, we demonstrate that 1 mM Na-caprate, a non-toxic concentration, increases the Leak Pathway permeability of a size range of fluorescein dextran molecules (4 kDa-40 kDa). Our data suggests that Na-caprate enhances permeability by increasing the number of Leak Pathway openings in confluent MDCK II cell populations without altering the opening size. Previous studies suggest Na-caprate increases paracellular permeability through the activation of phospholipase C (PLC). However, the addition of a PLC inhibitor, U73122, did not affect the ability of Na-caprate to increase paracellular permeability in MDCK II cell populations. In preliminary experiments, inhibition of ERK 1/2 activation with U0126 at least partially inhibited the Na-caprate effect. We are pursuing these findings to define the role of ERK 1/2 activation and the mechanism by which Na-caprate increases Leak Pathway permeability in the MDCK II cell populations.