Regulation of intracellular pH in the spontaneously hypertensive rat: Role of bicarbonate-dependent transporters

Josep Redon, Daniel Batlle*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Previous studies that have evaluated the Na+-H+ antiporter in cells from hypertensive subjects were generally performed under conditions in which HCO3-CO2, the physiological buffer system, was absent from the assay media. The objective of this study was to evaluate the activity of the Na+-H+ antiporter and that of the Na+-dependent and Na+-independent Cl--HCO3- exchangers in cells assayed in the presence of HCO3-CO2 in the media. Lymphocytes from 6- to 8-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats were obtained from the thymus gland and assayed immediately after isolation. The activity of the Na+-H+ antiporter after stimulation by cell acidification (pH(i) approximately 6.4) was similar in SHR and WKY rats (18.67±1.03 and 16.12±0.92 mmol H+/L per minute, respectively). Recovery from cell alkalinization was effected by an Na+- independent Cl--HCO3- exchanger, with maximal activity at an alkaline pH(i) (approximately 7.7). The stimulated activity of this Na+-independent Cl--HCO3- exchanger was also not different between SHR and WKY cells (2.65±0.25 and 2.55±0.32 mmol H+/L per minute, respectively). Acute chloride removal produced a rise in pH(i) that was Na+-dependent and sensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) but resistant to ethylisopropylamiloride (EIPA), reflecting the activity of an Na+-dependent Cl--HCO3- exchanger. Unlike the Na+-H+ exchanger and the Na+-independent Cl--HCO3- exchanger, which had their highest activities at extremes of pH(i) (low pH(i), Na+-H+ exchanger, and high pH(i), Na+- independent Cl--HCO3- exchanger), the Na+-dependent Cl--HCO3- exchanger had its maximal activity near steady-state pH(i) (approximately 7.1). No significant differences were found in the stimulated activity of this exchanger between cells from SHR and WKY rats (2.23±0.26 and 2.50±0.43 mmol H+/L per minute, respectively). The kinetic properties of the Na+- dependent and Na+-independent Cl--HCO3- exchanger, examined as a function of external Cl-, were also virtually identical in cells from SHR and WKY rats. We conclude that in lymphocytes from SHR and WKY rats, the activity of the two Cl--HCO3- exchangers, like that of the Na+-H+ exchanger, is dependent on the prevailing pH(i). The Na+-dependent Cl--HCO3- exchanger has its highest activity near steady-state pH(i), suggesting an important role in the cell defense against intracellular acidosis under physiological conditions. The similar kinetic properties in each of the two HCO3-- dependent transporters suggest that there are no intrinsic differences between lymphocytes from SHR and WKY rats with respect to the plasma membrane proteins that effect Cl--HCO3- exchange.

Original languageEnglish (US)
Pages (from-to)503-512
Number of pages10
Issue number4
StatePublished - Apr 1994


  • hydrogen-ion concentration
  • ion exchange
  • ion transport
  • rats, inbred SHR

ASJC Scopus subject areas

  • Internal Medicine


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