High sodium intake increases HCO-3 absorption in medullary thick ascending limb through adaptations in basolateral and apical Na+/H+ exchangers

David W. Good, Thampi George, Bruns A. Watts

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


A high sodium intake increases the capacity of the medullary thick ascending limb (MTAL) to absorb HCO-3. Here, we examined the role of the apical NHE3 and basolateral NHE1 Na+/H+ exchangers in this adaptation. MTALs from rats drinking H2O or 0.28 M NaCl for 5-7 days were perfused in vitro. High sodium intake increased HCO-3 absorption rate by 60%. The increased HCO-3 absorptive capacity was mediated by an increase in apical NHE3 activity. Inhibiting basolateral NHE1 with bath amiloride eliminated 60% of the adaptive increase in HCO-3 absorption. Thus the majority of the increase in NHE3 activity was dependent on NHE1. A high sodium intake increased basolateral Na+/H+ exchange activity by 89% in association with an increase in NHE1 expression. High sodium intake increased apical Na+/H+ exchange activity by 30% under conditions in which basolateral Na+/H+ exchange was inhibited but did not change NHE3 abundance. These results suggest that high sodium intake increases HCO-3 absorptive capacity in the MTAL through 1) an adaptive increase in basolateral NHE1 activity that results secondarily in an increase in apical NHE3 activity; and 2) an adaptive increase in NHE3 activity, independent of NHE1 activity. These studies support a role for NHE1 in the long-term regulation of renal tubule function and suggest that the regulatory interaction whereby NHE1 enhances the activity of NHE3 in the MTAL plays a role in the chronic regulation of HCO-3 absorption. The adaptive increases in Na+/H+ exchange activity and HCO3 absorption in the MTAL may play a role in enabling the kidneys to regulate acid-base balance during changes in sodium and volume balance.

Original languageEnglish (US)
Pages (from-to)F334-F343
JournalAmerican Journal of Physiology - Renal Physiology
Issue number2
StatePublished - Aug 2011


  • Acid-base balance
  • Kidney
  • NHE1
  • NHE3
  • Salt-sensitive hypertension

ASJC Scopus subject areas

  • Physiology
  • Urology

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