Differential regulation of membrane potential and conductance via intra- and extracellular pH in fused proximal tubular cells of frog kidney.

Intracellular pH (pH i ), membrane potential (V m ) and membrane conductance (G m ) in fused proximal tubular cells of the frog kidney, were determined at three extracellular pH (pH o ) values, 7.5, 8.5 and 6.5. Imposed changes of pH o by ±1 pH unit induced parallel but smaller shifts of pH i . The alkaline milieu hyperpolarized the cells and increased G m , whereas the acid milieu depolarized and lowered G m . We subsequently introduced a weak acid and its conjugate base (acetic acid/acetate), or a weak base and its conjugate acid (NH3/NH 4 + ), at pH o 7.5, 8.5 and 6.5 to shift pH i -without altering pH o , or to shift pH i against imposed changes of pH o . From these experiments, we observed that under some circumstances V m varied with pH o but without G m or pH i changes, whereas under other circumstances changes of G m occurred during alterations of pH i while pH o and V m remained unaltered. At pH i ≈ 6.5 associated with V m ≈ −10 mV, G m dramatically increased to quasi-infinite values. This increase was not an artifact since G m returned to its control value following recovery to the control solution or in the presence of hyperosmotic solution. In conclusion, we demonstrate a differential regulation whereby V m and G m are controlled by pH o and pH i : pH o modulates mainly V m , and pH i modulates chiefly G m . Furthermore, at pH i ≈ 6.5 and V m ≈ −10 mV, our data reveal a large G m that tends towards infinite values in a reversible fashion.