Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Oct;82(4):1366–1375. doi: 10.1172/JCI113740

5-(N,N-dimethyl)amiloride-sensitive Na-Li exchange in isolated specimens of human atrium.

H H Rasmussen 1, R D Harvey 1, E J Cragoe Jr 1, R E ten Eick 1
PMCID: PMC442693  PMID: 2459162

Abstract

To examine if a transmembrane Na-Li exchange similar to that reported to occur in human blood cells can be demonstrated in the heart, we incubated specimens of human atrium in cold (2-3 degrees C) Li-Tyrode's solution. The Li-loaded, Na-depleted specimens were then transferred to warm (30 degrees C) Na-Tyrode's solution. After transfer the membrane potential hyperpolarized to a level more negative than the equilibrium potential for K+. The hyperpolarization was inhibited by acetylstrophanthidin or K+-free solution indicating that it was due to current produced by the Na, K-pump responding to a Na load. This suggested that intracellular Li+ had been exchanged for Na+. The hyperpolarization was abolished by 10 microM 5-(N,N-dimethyl)amiloride while 10 microM bumetanide had no effect, findings that are consistent with the notion that the exchange of intracellular Li+ for extracellular Na+ occurs via an operational mode of the Na-H exchanger rather than being mediated through a mechanism involving the Na/K/2Cl cotransporter.

Full text

PDF
1366

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronson P. S. Red-cell sodium-lithium countertransport and essential hypertension. N Engl J Med. 1982 Jul 29;307(5):317–317. doi: 10.1056/NEJM198207293070517. [DOI] [PubMed] [Google Scholar]
  2. CARMELIET E. E. INFLUENCE OF LITHIUM IONS ON THE TRANSMEMBRANE POTENTIAL AND CATION CONTENT OF CARDIAC CELLS. J Gen Physiol. 1964 Jan;47:501–530. doi: 10.1085/jgp.47.3.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carmeliet E., Mubagwa K. Characterization of the acetylcholine-induced potassium current in rabbit cardiac Purkinje fibres. J Physiol. 1986 Feb;371:219–237. doi: 10.1113/jphysiol.1986.sp015970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chipperfield A. R. The (Na+-K+-Cl-) co-transport system. Clin Sci (Lond) 1986 Nov;71(5):465–476. doi: 10.1042/cs0710465. [DOI] [PubMed] [Google Scholar]
  5. DiFrancesco D. A new interpretation of the pace-maker current in calf Purkinje fibres. J Physiol. 1981 May;314:359–376. doi: 10.1113/jphysiol.1981.sp013713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Duhm J., Becker B. F. Studies on lithium transport across the red cell membrane. V. On the nature of the Na+-dependent Li+ countertransport system of mammalian erythrocytes. J Membr Biol. 1979 Dec 31;51(3-4):263–286. doi: 10.1007/BF01869087. [DOI] [PubMed] [Google Scholar]
  7. Dunham P. B., Senyk O. Lithium efflux through the Na/K pump in human erythrocytes. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3099–3103. doi: 10.1073/pnas.74.7.3099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edwards C. The selectivity of ion channels in nerve and muscle. Neuroscience. 1982 Jun;7(6):1335–1366. doi: 10.1016/0306-4522(82)90249-4. [DOI] [PubMed] [Google Scholar]
  9. Ehrlich B. E., Diamond J. M. Lithium, membranes, and manic-depressive illness. J Membr Biol. 1980;52(3):187–200. doi: 10.1007/BF01869189. [DOI] [PubMed] [Google Scholar]
  10. Eisner D. A., Lederer W. J. Na-Ca exchange: stoichiometry and electrogenicity. Am J Physiol. 1985 Mar;248(3 Pt 1):C189–C202. doi: 10.1152/ajpcell.1985.248.3.C189. [DOI] [PubMed] [Google Scholar]
  11. Eisner D. A., Lederer W. J., Vaughan-Jones R. D. The effects of rubidium ions and membrane potentials on the intracellular sodium activity of sheep Purkinje fibres. J Physiol. 1981 Aug;317:189–205. doi: 10.1113/jphysiol.1981.sp013820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gadsby D. C., Kimura J., Noma A. Voltage dependence of Na/K pump current in isolated heart cells. Nature. 1985 May 2;315(6014):63–65. doi: 10.1038/315063a0. [DOI] [PubMed] [Google Scholar]
  13. Glitsch H. G. Activation of the electrogenic sodium pump in guinea-pig auricles by internal sodium ions. J Physiol. 1972 Feb;220(3):565–582. doi: 10.1113/jphysiol.1972.sp009723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Grafe P., Rimpel J., Reddy M. M., ten Bruggencate G. Lithium distribution across the membrane of motoneurons in the isolated frog spinal cord. Pflugers Arch. 1982 Jun;393(4):297–301. doi: 10.1007/BF00581413. [DOI] [PubMed] [Google Scholar]
  15. Grinstein S., Rothstein A. Mechanisms of regulation of the Na+/H+ exchanger. J Membr Biol. 1986;90(1):1–12. doi: 10.1007/BF01869680. [DOI] [PubMed] [Google Scholar]
  16. Haas M., Schooler J., Tosteson D. C. Coupling of lithium to sodium transport in human red cells. Nature. 1975 Dec 4;258(5534):425–427. doi: 10.1038/258425a0. [DOI] [PubMed] [Google Scholar]
  17. Ives H. E., Yee V. J., Warnock D. G. Mixed type inhibition of the renal Na+/H+ antiporter by Li+ and amiloride. Evidence for a modifier site. J Biol Chem. 1983 Aug 25;258(16):9710–9716. [PubMed] [Google Scholar]
  18. Kahn A. M., Allen J. C., Cragoe E. J., Jr, Zimmer R., Shelat H. Sodium-lithium exchange in sarcolemmal vesicles from canine superior mesenteric artery. Circ Res. 1988 Mar;62(3):478–485. doi: 10.1161/01.res.62.3.478. [DOI] [PubMed] [Google Scholar]
  19. Kahn A. M. Difference between human red blood cell Na+-Li+ countertransport and renal Na+-H+ exchange. Hypertension. 1987 Jan;9(1):7–12. doi: 10.1161/01.hyp.9.1.7. [DOI] [PubMed] [Google Scholar]
  20. Mahnensmith R. L., Aronson P. S. The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes. Circ Res. 1985 Jun;56(6):773–788. doi: 10.1161/01.res.56.6.773. [DOI] [PubMed] [Google Scholar]
  21. NARAHASHI T., MOORE J. W., SCOTT W. R. TETRODOTOXIN BLOCKAGE OF SODIUM CONDUCTANCE INCREASE IN LOBSTER GIANT AXONS. J Gen Physiol. 1964 May;47:965–974. doi: 10.1085/jgp.47.5.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pandey G. N., Sarkadi B., Haas M., Gunn R. B., Davis J. M., Tosteson D. C. Lithium transport pathways in human red blood cells. J Gen Physiol. 1978 Aug;72(2):233–247. doi: 10.1085/jgp.72.2.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Piwnica-Worms D., Jacob R., Shigeto N., Horres C. R., Lieberman M. Na/H exchange in cultured chick heart cells: secondary stimulation of electrogenic transport during recovery from intracellular acidosis. J Mol Cell Cardiol. 1986 Nov;18(11):1109–1116. doi: 10.1016/s0022-2828(86)80036-0. [DOI] [PubMed] [Google Scholar]
  24. Rasmussen H. H., Singer D. H., Ten Eick R. E. Characterization of a sodium pump-induced hyperpolarization in isolated human atrium. Am J Physiol. 1986 Aug;251(2 Pt 2):H331–H339. doi: 10.1152/ajpheart.1986.251.2.H331. [DOI] [PubMed] [Google Scholar]
  25. Reuter H., Seitz N. The dependence of calcium efflux from cardiac muscle on temperature and external ion composition. J Physiol. 1968 Mar;195(2):451–470. doi: 10.1113/jphysiol.1968.sp008467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sariban-Sohraby S., Benos D. J. The amiloride-sensitive sodium channel. Am J Physiol. 1986 Feb;250(2 Pt 1):C175–C190. doi: 10.1152/ajpcell.1986.250.2.C175. [DOI] [PubMed] [Google Scholar]
  27. Sarkadi B., Alifimoff J. K., Gunn R. B., Tosteson D. C. Kinetics and stoichiometry of Na-dependent Li transport in human red blood cells. J Gen Physiol. 1978 Aug;72(2):249–265. doi: 10.1085/jgp.72.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schellenberg G. D., Anderson L., Cragoe E. J., Jr, Swanson P. D. Inhibition of synaptosomal membrane Na+-Ca2+ exchange transport by amiloride and amiloride analogues. Mol Pharmacol. 1985 May;27(5):537–543. [PubMed] [Google Scholar]
  29. Soltoff S. P., Mandel L. J. Amiloride directly inhibits the Na,K-ATPase activity of rabbit kidney proximal tubules. Science. 1983 May 27;220(4600):957–958. doi: 10.1126/science.6302840. [DOI] [PubMed] [Google Scholar]
  30. Ten Eick R., Nawrath H., McDonald T. F., Trautwein W. On the mechanism of the negative inotropic effect of acetylcholine. Pflugers Arch. 1976 Feb 24;361(3):207–213. doi: 10.1007/BF00587284. [DOI] [PubMed] [Google Scholar]
  31. Vigne P., Frelin C., Cragoe E. J., Jr, Lazdunski M. Structure-activity relationships of amiloride and certain of its analogues in relation to the blockade of the Na+/H+ exchange system. Mol Pharmacol. 1984 Jan;25(1):131–136. [PubMed] [Google Scholar]
  32. Wiggins J. R., Cranefield P. F. Effect on membrane potential and electrical activity of adding sodium to sodium-depleted cardiac purkinje fibers. J Gen Physiol. 1974 Oct;64(4):473–493. doi: 10.1085/jgp.64.4.473. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES