To study the ionic mechanisms of crosstalk between luminal and peritub
ular membranes induced by Na+-glucose cotransport in the proximal tubu
lar 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 bull
frog kidney. In control conditions with peritubular HCO3- (15 mM), lum
inal 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 abs
ence of peritubular HCO3- (HEPES-Ringer at constant pH), the luminal g
lucose produced a sustained increase in Na-i and suppression of pH(i)
elevation without affecting glucose-induced depolarization. Peritubula
r perfusion with DIDS (10(-4) M) abolished the change in pH(i) induced
by luminal glucose. Furthermore, the luminal glucose increased the tr
ansport number for K+ (g(K)/g(m)) in the peritubular membrane by 20%.
These results suggest that 1) glucose-induced depolarization suppresse
s peritubular HCO3- exit, followed by an elevation in pH(i), 2) the lu
minal glucose increases K+ conductance of the peritubular membrane, pr
obably by the elevation in pH(i), and 3) this increased K+ conductance
repolarizes the peritubular membrane, which can support the driving f
arce for Na+-glucose entry across the luminal membrane. Thus, we concl
ude that the crosstalk between peritubular and luminal membranes by Na
+-glucose cotransport is mainly modulated by changes in cell pH and me
mbrane potential in the proximal tubule.