Publications

• Kinetics and stoichiometry of Na-dependent Li transport in human red blood cells.

  Sarkadi B., Alifimoff J.K., Gunn R.B., Tosteson D.C.

  This paper describes the kinetics and stoichiometry of a tightly coupled Na-Li exchange transport system in human red cells. The system is inhibited by phloretin and furosemide but not by ouabain. Li influx by this system increases and saturates with increasing concentrations of external Li and in ... >> More

  This paper describes the kinetics and stoichiometry of a tightly coupled Na-Li exchange transport system in human red cells. The system is inhibited by phloretin and furosemide but not by ouabain. Li influx by this system increases and saturates with increasing concentrations of external Li and internal Na and is inhibited competitively by external Na. Comparable functions relate Li efflux and Na efflux to internal and external Li and Na concentrations. Analysis of these relations yields the following values for the ion concentrations required to half-maximally activate the transport system: internal Na and Li 9.0 and 0.5 mM, respectively, external Na and Li 25 and 1.5 mM, respectively. The system performs a 1:1 exchange of Na and Li moving in opposite directions across the red cell membrane. We found no evidence for a simultaneous transport of more than one Na and Li by the system. The maximum transport rate of Na-dependent Li transport varied between 0.1 and 0.37 mmol/(liter of cells X h) in the red cells of the five normal male subjects studied. No significant variations between individual subjects were observed for bicarbonate-stimulated Li transport and for the residual Li fluxes which occur in the absence of bicarbonate and in the presence of ouabain plus phloretin. << Less

  J Gen Physiol 72:249-265(1978) [PubMed] [EuropePMC]

• Expression of the human sodium/proton exchanger NHE-1 in Xenopus laevis oocytes enhances sodium/proton exchange activity and establishes sodium/lithium countertransport.

  Busch S., Burckhardt B.C., Siffert W.

  We investigated whether the human sodium/proton (Na+/H+) exchanger isoform 1 (NHE-1) can mediate sodium/lithium (Na+/Li+) countertransport. Using the Xenopus laevis oocyte expression system we determined amiloride-sensitive Li+ uptake, a measure of Na+/H+ exchange, in oocytes injected with water o ... >> More

  We investigated whether the human sodium/proton (Na+/H+) exchanger isoform 1 (NHE-1) can mediate sodium/lithium (Na+/Li+) countertransport. Using the Xenopus laevis oocyte expression system we determined amiloride-sensitive Li+ uptake, a measure of Na+/H+ exchange, in oocytes injected with water or NHE-1 cRNA. Amiloride-sensitive Li+ uptake was three-to tenfold enhanced over control in NHE-1 cRNA-injected cells and was selectively inhibited by 0.01 microM HOE 694 [i.e. (3-methylsulphonyl-4-piperidinobenzoyl) guanidine methanesulphonate]. The endogenously present Na+/H+ exchanger was insensitive to HOE 694. After acidification of oocytes from pH 7.7 to 6.8, amiloride-sensitive Li+ uptake was four-to tenfold higher in NHE-1 cRNA-injected cells than in controls. Li+ efflux from control oocytes was independent of extracellular Na+, indicating that these cells expressed no measurable Na+/Li+ countertransport activity. In NHE-1 cRNA-injected oocytes, Li+ efflux was distinctly enhanced by extracellular Na+ ions. This Na(+)-dependent Li+ efflux was inhibited by ethylisopropylamiloride, phloretin and by cytosolic acidification. The data show that expression of the NHE-1 in X. laevis oocytes induces the expression of Na+/Li+ countertransport. The data confirm that Na+/H+ exchange and Na+/Li+ countertransport are mediated by the same transport system. << Less

  Pflugers Arch. 429:859-869(1995) [PubMed] [EuropePMC]

• Unconventional chemiosmotic coupling of NHA2, a mammalian Na+/H+ antiporter, to a plasma membrane H+ gradient.

  Kondapalli K.C., Kallay L.M., Muszelik M., Rao R.

  Human NHA2, a newly discovered cation proton antiporter, is implicated in essential hypertension by gene linkage analysis. We show that NHA2 mediates phloretin-sensitive Na(+)-Li(+) counter-transport (SLC) activity, an established marker for hypertension. In contrast to bacteria and fungi where H( ... >> More

  Human NHA2, a newly discovered cation proton antiporter, is implicated in essential hypertension by gene linkage analysis. We show that NHA2 mediates phloretin-sensitive Na(+)-Li(+) counter-transport (SLC) activity, an established marker for hypertension. In contrast to bacteria and fungi where H(+) gradients drive uptake of metabolites, secondary transport at the plasma membrane of mammalian cells is coupled to the Na(+) electrochemical gradient. Our findings challenge this paradigm by showing coupling of NHA2 and V-type H(+)-ATPase at the plasma membrane of kidney-derived MDCK cells, resulting in a virtual Na(+) efflux pump. Thus, NHA2 functionally recapitulates an ancient shared evolutionary origin with bacterial NhaA. Although plasma membrane H(+) gradients have been observed in some specialized mammalian cells, the ubiquitous tissue distribution of NHA2 suggests that H(+)-coupled transport is more widespread. The coexistence of Na(+) and H(+)-driven chemiosmotic circuits has implications for salt and pH regulation in the kidney. << Less

  J. Biol. Chem. 287:36239-36250(2012) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Sodium-lithium exchange and sodium-proton exchange are mediated by the same transport system in sarcolemmal vesicles from bovine superior mesenteric artery.

  Kahn A.M., Allen J.C., Cragoe E.J. Jr., Shelat H.

  Several laboratories have reported that Na+-Li+ countertransport activities are increased in red blood cells from patients with essential hypertension. It has been proposed that the activity of this red blood cell transport system might reflect the activity of a similar system in vascular smooth m ... >> More

  Several laboratories have reported that Na+-Li+ countertransport activities are increased in red blood cells from patients with essential hypertension. It has been proposed that the activity of this red blood cell transport system might reflect the activity of a similar system in vascular smooth muscle. We previously demonstrated Na+-Li+ exchange in sarcolemmal vesicles from canine artery and proposed that this transport function might be mediated by the Na+-H+ exchanger. In the present studies, however, we were unable to demonstrate Na+-Li+ countertransport in canine red blood cells. Since bovine red blood cells have a vigorous Na+-Li+ exchanger and we previously demonstrated Na+-H+ exchange in sarcolemmal vesicles from bovine artery, we wished to determine whether bovine sarcolemmal vesicles mediate Na+-Li+ exchange and whether this transport function is mediated via the Na+-H+ exchanger. We found that an outwardly directed proton or Li+ gradient stimulated 22Na+ uptake in sarcolemmal vesicles from bovine superior mesenteric artery. Li+ gradient-stimulated Na+ uptake was not due to electrical coupling between the two ions, was not affected by a change in membrane potential, and could not be explained by the parallel operation of Li+-H+ and Na+-H+ exchange. External Li+ inhibited proton gradient-stimulated Na+ uptake, and external protons inhibited Li+ gradient-stimulated Na+ uptake. Na+ efflux from vesicles was stimulated by inwardly directed gradients for Li+ or protons, and these effects were not additive. Proton efflux from vesicles was stimulated by inwardly directed gradients for Na+ or Li+, and these effects were not additive. Finally, Na+-H+ exchange and Na+-Li+ exchange in sarcolemmal vesicles were inhibited by 5-(N-ethyl-N-isopropyl)amiloride in an identical dose-dependent manner. In conclusion, Na+-Li+ countertransport could not be demonstrated in canine red blood cells, but as is the case with bovine red blood cells, sarcolemmal vesicles from bovine artery mediate Na+-Li+ countertransport. This transport function and sarcolemmal Na+-H+ exchange are mediated via a single 5-(N-ethyl-N-isopropyl)amiloride-sensitive cation exchanger with affinity for Na+, Li+, and protons. The cow, as opposed to the dog, may be a good animal model to test whether the activity of red blood cell Na+-Li+ countertransport is predictive of the activity of Na+-Li+ (and Na+-H+) exchange in vascular smooth muscle. << Less

  Circ Res 65:818-828(1989) [PubMed] [EuropePMC]