Hydrogen ion permeability of the rabbit proximal convoluted tubule

Acidification of luminal fluid in the proximal convoluted tubule has been modeled as a pump-leak system. Using isolated perfused rabbit proximal convoluted tubules in a HCO-3/CO2-free in vitro environment, we studied "H+ leak" by imposing pH gradients across the tubule and measuring the change in pH from perfusate to collected fluid. Active acidification was inhibited by acetazolamide with and without hypothermia. At 21 degrees C a symmetrical H+ leak with an apparent permeability coefficient of approximately 0.15 cm X s-1 was found with either a lumen-to-bath or bath-to-lumen [H+] gradient. At 37 degrees C a much higher apparent permeability coefficient was found that was dependent on luminal lactate. Phosphate movement did not affect H+ fluxes significantly. Without luminal lactate, the apparent permeability coefficient was 0.31 cm X s-1. Although this permeability coefficient is larger than other ionic permeability coefficients in this segment, it is not sufficient to account for a significant H+ leak compared with rates of acidification or bicarbonate reabsorption. To investigate the role of Na+-H+ exchange in mediating the observed H+ leak, we perfused tubules with low [Na+] solutions with and without amiloride (10(-3) M). Neither the lower [Na+] nor the presence of amiloride diminished the apparent [H+] permeability coefficient. We conclude that a H+ leak pathway independent of Na+-H+ exchange is present in the proximal convoluted tubule.