Effect of norepinephrine on intracellular pH in kidney proximal tubule:: role of Na+-(HCO3-)n cotransport

We examined the effect of norepinephrine (NE) on intracellular pH (pH(i)) and activity of Na(+) (a(i)(Na)) in the isolated perfused kidney proximal tubule of Ambystoma, using single-barreled voltage and ion-selective microelectrodes. In control HCO, Ringer, addition of 10(-6) M NE to the bath reversibly depolarized the basolateral membrane potential (V(1)), the luminal membrane potential (V(2)), and the transepithelial potential difference (V(3)) and increased pH(i) by 0.14 +/- 0.02. These effects were mimicked by isoproterenol but were abolished after pretreatment with SITS or in the absence of CO(2)/HCO(3)(-). Removal of bath Na(+) depolarized V(1) and V(2), hyperpolarized V(3), and decreased pH(i). These effects are largely mediated by the electrogenic Na(+)-(HCO(3)(-))(n) cotransporter. In the presence of NE, the effects of Na(+) removal on membrane potential differences and the rate of change of pH(i) were significantly smaller. Reducing bath HCO(3)(-) concentration from 10 to 2 mM at constant CO(2) (pH 6.8) depolarized V(1) and V(2), decreased pH(i), and lowered a(i)(Na). These changes are also due to Na(+)-(HCO(3)(-))(n). In the presence of NE, reducing bath [HCO(3)(-)] caused a smaller depolarizations of V(1) and V(2) and the rate of pH(i) decrease was significantly reduced. Our results indicate: 1) NE causes an increase in pH(i); 2) the NE-induced alkalinization is mediated by a SITS-sensitive and HCO(3)(-)-dependent transporter on the basolateral membrane; and 3) in the presence of NE, the reduced effects caused by basolateral HCO(3)(-) changes or Na(+) removal are indicative of an inhibitory effect of NE on Na(+)-(HCO(3)(-))(n) cotransport.