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Department of Physiology, University of Otago Medical School, Dunedin, New Zealand.

1. The effects of changes in media osmolality on the transepithelial current through the toad urinary bladder under voltage-clamp conditions have been studied. Over the limited range (+/- 24 mosmol/kg H2O) used in these investigations, changes in the osmolality of the mucosal bathing fluid produced no changes in transepithelial current. 2. Changes in osmolality of the serosal fluid greatly affected the transepithelial current with a decrease (increase) in osmolality producing a sustained increase (decrease) in current. 3. The changes in steady-state current were approximately proportional to the magnitude of the osmotic steps and were reproducible and reversible if the osmolalities of the solutions were confined to a domain of 220-260 mosmol/kg H2O. 4. Amiloride, which was used to block all active current, also eliminated the electrical responses to an osmotic pulse, indicating that the responses were of cellular origin. 5. The effects of substituting gluconate for medium chloride were examined. Similar responses were observed, indicating that they were not due to changes in a plasma membrane chloride conductance. 6. The transient currents observed during the changes from one steady state to the other often contained an oscillatory component, the amplitude and the degree of damping of which varied between bladders. The amplitude of the oscillations, but not their frequency, could be varied by altering the magnitude of the osmotic pulse and by changing the imposed transepithelial voltage. Decreasing the electrical potential of the mucosal solution with respect to that of the serosal solution decreased the amplitude of the oscillations, as did increased serosal potassium or substitution of gluconate for serosal chloride. The period of the oscillations always remained within the range of 9-12 min. 7. The results suggest that two major processes are initiated by an osmotic step in the serosal bathing medium. The first involves the establishment of new ion gradients and the second, alterations in sodium pump activity. In addition, there is evidence for a voltage-dependent sodium conductance in the apical membrane.

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