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. 1994 Dec 1;481(Pt 2):279–291. doi: 10.1113/jphysiol.1994.sp020438

The effect of cardiac glycosides on the Na+ pump current-voltage relationship of isolated rat and guinea-pig heart cells.

A N Hermans 1, H G Glitsch 1, F Verdonck 1
PMCID: PMC1155928  PMID: 7738826

Abstract

1. Whole-cell recording from isolated rat and guinea-pig ventricular myocytes revealed a change of the cardiac Na+ pump current (Ip)-voltage (V) relationship by cardiac glycosides, specific inhibitors of the Na(+)-K+ pump. 2. Dihydro-ouabain (DHO) diminished Ip in rat ventricular cells at 0 mV in a concentration-dependent manner. 3. The concentration-response curve of Ip inhibition caused by DHO was shifted to higher [DHO] at higher extracellular K+ concentrations ([K+]o) or at more negative membrane potentials. 4. In rat myocytes, DHO immediately flattened the normalized cardiac Ip-V curve and evoked or enhanced a region of negative slope. 5. Ouabain, at concentrations which caused a comparable inhibition of Ip, exerted DHO-like effects on the Ip-V relationship of rat ventricular myocytes. However, the effects developed more slowly. 6. A slowly developing alteration of the Ip-V curve was also observed upon application of DHO to guinea-pig ventricular cells. The range of [DHO] used was about 100-fold lower than that applied to rat ventricular cells, but was equally effective for Ip inhibition. 7. Increasing the K+ concentration of DHO-containing media affected the existing equilibrium of DHO binding to the cardiac Na(+)-K+ pump. A new equilibrium was reached within about 3 s in rat ventricular myocytes, but only within about 50 s in guinea-pig ventricular cells under the experimental conditions chosen. 8. It is concluded that the changes of the cardiac Ip-V curve induced by cardiac glycosides are mediated by voltage-dependent variations of the local [K+]o at the K+ binding sites of the Na(+)-K+ pump in an 'access channel'. The variations were estimated by means of the Boltzmann equation. The estimations agreed with those derived from the measured DHO binding to the Na(+)-K+ pump at various [K+]o. A new equilibrium of glycoside binding to the pump is established at the altered [K+]o. The time necessary to reach the new binding equilibrium varies with the cardioactive steroid, its concentration and the glycoside sensitivity of the cardiac cells.

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Selected References

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

  1. Bielen F. V., Glitsch H. G., Verdonck F. Changes of the subsarcolemmal Na+ concentration in internally perfused cardiac cells. Biochim Biophys Acta. 1991 Jun 18;1065(2):269–271. doi: 10.1016/0005-2736(91)90239-5. [DOI] [PubMed] [Google Scholar]
  2. Bielen F. V., Glitsch H. G., Verdonck F. Dependence of Na+ pump current on external monovalent cations and membrane potential in rabbit cardiac Purkinje cells. J Physiol. 1991 Oct;442:169–189. doi: 10.1113/jphysiol.1991.sp018788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bielen F. V., Glitsch H. G., Verdonck F. Na+ pump current-voltage relationships of rabbit cardiac Purkinje cells in Na(+)-free solution. J Physiol. 1993 Jun;465:699–714. doi: 10.1113/jphysiol.1993.sp019701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bielen F. V., Glitsch H. G., Verdonck F. The kinetics of the inhibition by dihydroouabain of the sodium pump current in single rabbit cardiac Purkinje cells. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jan;345(1):100–107. doi: 10.1007/BF00175476. [DOI] [PubMed] [Google Scholar]
  5. Gadsby D. C., Nakao M. Steady-state current-voltage relationship of the Na/K pump in guinea pig ventricular myocytes. J Gen Physiol. 1989 Sep;94(3):511–537. doi: 10.1085/jgp.94.3.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  7. Nakao M., Gadsby D. C. [Na] and [K] dependence of the Na/K pump current-voltage relationship in guinea pig ventricular myocytes. J Gen Physiol. 1989 Sep;94(3):539–565. doi: 10.1085/jgp.94.3.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Rakowski R. F., Gadsby D. C., De Weer P. Stoichiometry and voltage dependence of the sodium pump in voltage-clamped, internally dialyzed squid giant axon. J Gen Physiol. 1989 May;93(5):903–941. doi: 10.1085/jgp.93.5.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Rakowski R. F., Vasilets L. A., LaTona J., Schwarz W. A negative slope in the current-voltage relationship of the Na+/K+ pump in Xenopus oocytes produced by reduction of external [K+]. J Membr Biol. 1991 Apr;121(2):177–187. doi: 10.1007/BF01870531. [DOI] [PubMed] [Google Scholar]
  10. Vasilets L. A., Ohta T., Noguchi S., Kawamura M., Schwarz W. Voltage-dependent inhibition of the sodium pump by external sodium: species differences and possible role of the N-terminus of the alpha-subunit. Eur Biophys J. 1993;21(6):433–443. doi: 10.1007/BF00185871. [DOI] [PubMed] [Google Scholar]
  11. Vasilets L. A., Schwarz W. Regulation of endogenous and expressed Na+/K+ pumps in Xenopus oocytes by membrane potential and stimulation of protein kinases. J Membr Biol. 1992 Jan;125(2):119–132. doi: 10.1007/BF00233352. [DOI] [PubMed] [Google Scholar]

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