Effect of norepinephrine on intracellular pH in kidney proximal tubule: role of Na+- (HCO-3) n cotransport
Abdulnour-Nakhoul, S.; Khuri, R.N.; Nakhoul, N.L.
American Journal of Physiology 275(1): F33-F45
1998
ISSN/ISBN: 0002-9513 PMID: 9689002 Document Number: 486384
We examined the effect of norepinephrine (NE) on intracellular pH (pHi) and activity of Na+ (aiNa) in the isolated perfused kidney proximal tubule of Ambystoma, using single-barreled voltage and ion-selective microelectrodes. In control HCO3- Ringer, addition of 10-6 M NE to the bath reversibly depolarized the basolateral membrane potential (V1), the luminal membrane potential (V2), and the transepithelial potential difference (V3) and increased pHi by 0.14 ± 0.02. These effects were mimicked by isoproterenol but were abolished after pretreatment with SITS or in the absence of CO2/HCO3-. Removal of bath Na+ depolarized V1 and V2, hyperpolarized V3, and decreased pHi. These effects are largely mediated by the electrogenic Na+-(HCO3-)n cotransporter. In the presence of NE, the effects of Na+ removal on membrane potential differences and the rate of change of pHi were significantly smaller. Reducing bath HCO3- concentration from 10 to 2 mM at constant CO2 (pH 6.8) depolarized V1 and V2, decreased pHi, and lowered aiNa. These changes are also due to Na+-(HCO3-)n. In the presence of NE, reducing bath caused a smaller depolarizations of V1 and V2, and the rate of pHi decrease was significantly reduced. Our results indicate: 1) NE causes an increase in pHi; 2) the NE-induced alkalinization is mediated by a SITS-sensitive and HCO3--dependent transporter on the basolateral membrane; and 3) in the presence of NE, the reduced effects caused by basolateral HCO3- changes or Na+ removal are indicative of an inhibitory effect of NE on Na+-(HCO3-)n cotransport. Reprinted by permission of the publisher.