PROXIMAL TUBULAR CELL ALKALINIZATION INDUCED BY NA+-GLUCOSE COTRANSPORT

To study the ionic mechanisms of crosstalk between luminal and peritubular membranes induced by Na+-glucose cotransport in the proximal tubular cells, we applied the ion-selective microelectrode techniques and measured intracellular ion activities of Na+ (Na-i) and H+ (pH(i)), as well as peritubular membrane potential (E(M)) in doubly-perfused bullfrog kidney. In control conditions with peritubular HCO3- (15 mM), luminal perfusion with 10 mM D-glucose induced a 12 mV depolarization of peritubular membrane (glucose-induced depolarization) with a transient increase in Na-i by 3 mM and an elevation in pH(i) by 0.1. In the absence of peritubular HCO3- (HEPES-Ringer at constant pH), the luminal glucose produced a sustained increase in Na-i and suppression of pH(i) elevation without affecting glucose-induced depolarization. Peritubular perfusion with DIDS (10(-4) M) abolished the change in pH(i) induced by luminal glucose. Furthermore, the luminal glucose increased the transport number for K+ (g(K)/g(m)) in the peritubular membrane by 20%. These results suggest that 1) glucose-induced depolarization suppresses peritubular HCO3- exit, followed by an elevation in pH(i), 2) the luminal glucose increases K+ conductance of the peritubular membrane, probably by the elevation in pH(i), and 3) this increased K+ conductance repolarizes the peritubular membrane, which can support the driving farce for Na+-glucose entry across the luminal membrane. Thus, we conclude that the crosstalk between peritubular and luminal membranes by Na+-glucose cotransport is mainly modulated by changes in cell pH and membrane potential in the proximal tubule.