Feedback inhibition of sodium uptake in K+-depolarized toad urinary bladders.

Ouabain-blocked toad urinary bladders were maintained in Na+-free mucosal solutions, and a depolarizing solution of high K+ activity containing only 5 mM Na+ on the serosal side. Exposure to mucosal sodium (20 mM activity) evoked a transient amiloride-blockable inward current, which decayed to near zero within one hour. The apical sodium conductance increased in the initial phase of the current decay and decreased in the second phase. The conductance decrease required Ca2+ to be present on the serosal side and was more rapid when the mucosal Na+ activity was higher. At 20 mM mucosal Na+ and 3 mM serosal Ca2+ the initial (maximal) rate of inhibition amounted to 20% in 10 min. The conductance decrease could be accelerated by raising the serosal Ca2+ activity to 10 mM. The inhibition reversed on lowering the serosal Ca2+ to 3 microM and, in addition, the mucosal Na+ to zero. Exposure of the mucosal surface to the ionophore nystatin abolished the Ca2+ sensitivity of the transcellular conductance, showing that the Ca2+-sensitive conductance resides in the apical membrane. The data imply that in the K+-depolarized epithelia, cellular Ca2+, taken up from the serosal medium by means of a Na+-Ca2+ antiport, cause feedback inhibition by blockage of apical Na+ channels. However, the rate of inhibition is small, such that this regulatory mechanism will have little effect at 1 mM serosal Ca2+ and less than 20 mM cellular Na+.