To examine the pathways of K permeation in the cortical collecting duct (CCD) from K-restricted rabbits, we studied the effects of the following three maneuvers: 1) luminal amiloride addition; 2) luminal Ba addition; and 3) luminal Na removal. Luminal addition of amiloride (1 mM) significantly increased the 86Rb lumen-to-bath efflux coefficient (KRb), and this effect was fully blocked by the presence of 2 mM luminal Ba. Addition of 2 mM luminal Ba reduced KRb both in the absence of luminal Na and in the presence of luminal Na. In contrast to the effect of amiloride addition, removal of luminal Na significantly increased KRb, but neither 2 mM luminal Ba nor 4 mM luminal Ba totally abolished this effect. However, simultaneous addition of luminal Ba and Sch 28080 (10 microM) fully inhibited the increase in KRb upon luminal Na removal, indicating that luminal Na removal enhances Rb efflux in part via H-K-adenosinetriphosphatase (H-K-ATPase). To test whether Na acts as a partial agonist for cation efflux via the H-K-ATPase we examined the effect of Sch 28080 on the 22Na lumen-to-bath efflux coefficient (KNa). These studies were conducted in the presence of 0.1 mM luminal amiloride to block fully apical conductive Na efflux, and the effect of Sch 28080 on KNa was examined at two different ambient K concentrations. In the presence of 0.5 mM K, Sch 28080 (10 microM) significantly inhibited KNa from 47.6 +/- 4.8 to 35.0 +/- 6.8 nm/s (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)