Evidence from renal proximal tubules that HC[O.sup.-.sub.3] and solute reabsorption are acutely regulated not by pH but by basolateral HC[O.sup.-.sub.3] and C[O.sub.2]

Respiratory acidosis, a decrease in blood pH caused by a rise in [C[O.sub.2]], rapidly triggers a compensatory response in which the kidney markedly increases its secretion of [H.sup.+] from blood to urine. However, in this and other acid-base disturbances, the equilibrium C[O.sub.2] + [H.sub.2]O [??] HC[O.sup.-.sub.3] + [H.sup.+] makes it impossible to determine whether the critical parameter is [C[O.sub.2]], [HC[O.sup.-.sub.3]], and/or pH. Here, we used out-of-equilibrium C[O.sub.2]/HC[O.sup.-.sub.3] solutions to alter basolateral (BL) [HC[O.sup.-.sub.3]], [C[O.sub.2]], or pH, systematically and one at a time, on isolated perfused S2 rabbit proximal tubules. We found that increasing [[HC[O.sup.-.sub.3]]BL] from 0 to 44 mM, at a fixed [[C[O.sub.2]]BL] of 5% and a fixed [pH.sub.BL] of 7.40, caused HC[O.sup.-.sub.3] reabsorption ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.]) to fall by half but did not significantly affect volume reabsorption ([J.sub.V]). Increasing [[C[O.sub.2]]BL] from 0% to 20%, at a fixed [[HC[O.sup.-.sub.3]]BL] of 22 mM and [pH.sub.BL] of 7.40, caused [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.] to rise 2.5-fold but did not significantly affect [J.sub.V]. Finally, increasing [pH.sub.BL] from 6.80 to 8.00, at a fixed [[HC[O.sup.-.sub.3]]BL] of 22 mM and [[C[O.sub.2]]BL] of 5%, did not affect either [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.] or [J.sub.V]. Analysis of the [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.] and [J.sub.V] data implies that, as the tubule alters [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.], it compensates the reabsorption of other solutes to keep [J.sub.V] approximately constant. Because the cells cannot respond acutely to pH changes, we propose that the responses of [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.] and the reabsorption of other solutes to changes in [[HC[O.sup.-.sub.3]]BL] or [[C[O.sub.2]]BL] involve sensors for basolateral HC[O.sup.-.sub.3] and C[O.sub.2]. kidney | out-of-equilibrium solution | acid-base disturbances | volume reabsorption