Proximal tubule volume regulation in hyperosmotic media: Intracellular K⁺, Na⁺, and Cl^-

Nonperfused proximal S2 segments from rabbit kidney cortex have been shown to keep cell volume constant as medium osmolality is slowly raised but to shrink and not exhibit regulatory volume increase (RVI) if medium osmolality is abruptly elevated (J. Lohr and J. Grantham. J. Clin. Invest. 78: 1165-1172, 1986). In the current study, 0.5 mM butyrate in the medium 1) extended the range from 361 to 450 mosmol/kgH₂O over which cells maintained volume constant as osmolality was gradually raised and 2) restored RVI after cell shrinkage when osmolality was rapidly raised from 295 to 400 mosmol/kgH₂O. Volume regulation was associated with net increases in intracellular Na⁺ and Cl^- but no change in K⁺ (measured by electron probe). The increments in Na⁺ and Cl^- were insufficient to account for the total addition of osmolytes required for volume maintenance or restoration. The fraction of the expected increase in intracellular osmoles accounted for by the increase in [(K⁺)(i) + (Na⁺)(i) + (Cl^-)(i)] was 52 and 21% for gradual and rapid osmotic changes, respectively. We conclude that butyrate enhances the capacity of S2 segments to regulate volume in hyperosmotic medium by promoting addition of Na⁺ and Cl^- and by other undetermined factors.