Effect of PO2 and metabolic inhibitors on ionic fluxes across the isolated rabbit corneal endothelium.

Bicarbonate and sodium fluxes were measured across the isolated rabbit corneal endothelium under the influence of several inhibitors. Depression of PO2 in the bathing medium decreased net sodium movement but increased bicarbonate movement. Furosemide did not alter bicarbonate fluxes at either 10(-4) or 10(-5) M, but increased passive sodium flux leading to a decrease in net flux. Thiocyanate, at 5 x 10(-3) or 5 x 10(-2) M, decreased active bicarbonate flux and hence net flux, but had no effect on sodium fluxes. Dinitrophenol increased only the passive bicarbonate flux while decreasing both active and passive sodium fluxes, albeit unequally, leading to a decreased net flux. Ethacrynic acid affected only passive bicarbonate flux, while decreasing net sodium flux. The stilbene derivatives, SITS and DIDS caused opposite effects on both sodium and bicarbonate fluxes. SITS decreased net bicarbonate flux by decreasing active and increasing passive flux, yet increased net sodium flux. DIDS, however, increased net bicarbonate flux but decreased net sodium flux. The results may be explained by current models for endothelial ion transport that include a Na+/H+ antiport and a HCO3-/Na+ symport system in parallel with an independent pathway for HCO3- exit from the endothelial cells. When compared with prior corneal swelling data using these same inhibitors, the maintenance of corneal thickness appears to be dependent on the variation of ion fluxes from normal values, and the dissociation of the two active ion fluxes. In addition, there appears to be a significant ability of ion transport systems to compensate for disturbances to other ion exchange or transport mechanisms.