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.