Electrophysiology of succinate transport across rabbit renal brush border membranes

In rabbit renal brush border membrane vesicles, the membrane potential was monitored using a voltage-sensitive optical probe (diS-C3-(5)). The ionic dependence of the electrogenic Na+/succinate co-transporter was determined in the presence of monovalent anions and mono-, di-, and trivalent cations. Na+ and La3+ were the only cations capable of supporting a succinate-dependent membrane depolarization: Li+, K+, Rb+, Cs+, NH4+, Hg2+, Ca2+, Ba2+, Sr2+, Mg2+, Cu2+, Fe2+, Cd2+, Be2+, Pb2+, Zn2+, Mn2+ and Co2+ did not. Succinate increased the Na+ permeability of the brush border membrane in a saturable manner: saturating succinate (3 mM) concentrations increased the Na+/K+ permeability (PNa/PK) ratio from 0.6 to 2.3. In the presence of Na+, Li+ and Hg2+ inhibit the succinate potential: cis-Li+ inhibition is competitive with an apparent Ki of 2 mM, while trans-Li+ is noncompetitive; cis-Hg2+ decreased the maximal depolarization with an inhibitor constant Ki of 8 microM, and this effect was irreversible. Cations having no effect included K+, Rb+, Cs+, NH4+, Ba2+, Ca2+, Mg2+, Sr2+, Cu2+, Fe2+, Cd2+, Co2+, Be2+, Zn2+, Pb2+, Mn2+, and La3+. It is concluded that succinate/Na+ co-transport produces a specific increase in the Na+ conductance of renal brush borders.