Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Jan 1;89(1):99–103. doi: 10.1073/pnas.89.1.99

The cardiac conduction system in the rat expresses the alpha 2 and alpha 3 isoforms of the Na+,K(+)-ATPase.

R Zahler 1, M Brines 1, M Kashgarian 1, E J Benz Jr 1, M Gilmore-Hebert 1
PMCID: PMC48183  PMID: 1309618

Abstract

The sodium pump is crucial for the function of the heart and of the cardiac conduction system, which initiates the heartbeat. The alpha (catalytic) subunit of this pump has three isoforms; the alpha 1 isoform is ubiquitous, but the alpha 2 and alpha 3 isoforms are localized to excitable tissue. Because rodent alpha 2 and alpha 3 isoforms are relatively sensitive to ouabain, which also slows cardiac conduction, we studied heart-cell-specific expression of pump isoform genes. Multiple conduction-system structures, including sinoatrial node, bundle branches, and Purkinje strands, had prominent, specific hybridization signal for alpha 2 and alpha 3 isoforms compared with adjacent working myocytes. This gene-expression approach may be useful for labeling conduction tissue and also for localizing specific membrane channels and receptors in this system.

Full text

PDF

Images in this article

Selected References

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

  1. Charlemagne D., Maixent J. M., Preteseille M., Lelievre L. G. Ouabain binding sites and (Na+,K+)-ATPase activity in rat cardiac hypertrophy. Expression of the neonatal forms. J Biol Chem. 1986 Jan 5;261(1):185–189. [PubMed] [Google Scholar]
  2. Cohen I. S., Datyner N. B., Gintant G. A., Mulrine N. K., Pennefather P. Properties of an electrogenic sodium-potassium pump in isolated canine Purkinje myocytes. J Physiol. 1987 Feb;383:251–267. doi: 10.1113/jphysiol.1987.sp016407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gilmore-Hebert M., Mercer R. W., Schneider J. W., Benz E. J. In vitro expression of the alpha and beta subunits of the Na,K-ATPase. Prog Clin Biol Res. 1988;268B:71–76. [PubMed] [Google Scholar]
  4. Herrera V. L., Chobanian A. V., Ruiz-Opazo N. Isoform-specific modulation of Na+, K+-ATPase alpha-subunit gene expression in hypertension. Science. 1988 Jul 8;241(4862):221–223. doi: 10.1126/science.2838907. [DOI] [PubMed] [Google Scholar]
  5. Iacono G., Vassalle M. On the mechanism of the different sensitivity of Purkinje and myocardial fibers to strophanthidin. J Pharmacol Exp Ther. 1990 Apr;253(1):1–12. [PubMed] [Google Scholar]
  6. Lucchesi P. A., Sweadner K. J. Postnatal changes in Na,K-ATPase isoform expression in rat cardiac ventricle. Conservation of biphasic ouabain affinity. J Biol Chem. 1991 May 15;266(14):9327–9331. [PubMed] [Google Scholar]
  7. Maixent J. M., Charlemagne D., de la Chapelle B., Lelievre L. G. Two Na,K-ATPase isoenzymes in canine cardiac myocytes. Molecular basis of inotropic and toxic effects of digitalis. J Biol Chem. 1987 May 15;262(14):6842–6848. [PubMed] [Google Scholar]
  8. Matsuda T., Iwata H., Cooper J. R. Specific inactivation of alpha (+) molecular form of (Na+ + K+)-ATPase by pyrithiamin. J Biol Chem. 1984 Mar 25;259(6):3858–3863. [PubMed] [Google Scholar]
  9. Ng Y. C., Akera T. Two classes of ouabain binding sites in ferret heart and two forms of Na+-K+-ATPase. Am J Physiol. 1987 May;252(5 Pt 2):H1016–H1022. doi: 10.1152/ajpheart.1987.252.5.H1016. [DOI] [PubMed] [Google Scholar]
  10. Nowak G., Haustein K. O. Different toxic effects of ouabain and 16-epi-gitoxin on Purkinje fibres and ventricular muscle fibres. Pharmacology. 1976;14(3):256–264. doi: 10.1159/000136603. [DOI] [PubMed] [Google Scholar]
  11. Orlowski J., Lingrel J. B. Differential expression of the Na,K-ATPase alpha 1 and alpha 2 subunit genes in a murine myogenic cell line. Induction of the alpha 2 isozyme during myocyte differentiation. J Biol Chem. 1988 Nov 25;263(33):17817–17821. [PubMed] [Google Scholar]
  12. Orlowski J., Lingrel J. B. Tissue-specific and developmental regulation of rat Na,K-ATPase catalytic alpha isoform and beta subunit mRNAs. J Biol Chem. 1988 Jul 25;263(21):10436–10442. [PubMed] [Google Scholar]
  13. Schneider J. W., Mercer R. W., Caplan M., Emanuel J. R., Sweadner K. J., Benz E. J., Jr, Levenson R. Molecular cloning of rat brain Na,K-ATPase alpha-subunit cDNA. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6357–6361. doi: 10.1073/pnas.82.18.6357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schneider J. W., Mercer R. W., Gilmore-Hebert M., Utset M. F., Lai C., Greene A., Benz E. J., Jr Tissue specificity, localization in brain, and cell-free translation of mRNA encoding the A3 isoform of Na+,K+-ATPase. Proc Natl Acad Sci U S A. 1988 Jan;85(1):284–288. doi: 10.1073/pnas.85.1.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sherf L., James T. N. Fine structure of cells and their histologic organization within internodal pathways of the heart: clinical and electrocardiographic implications. Am J Cardiol. 1979 Aug;44(2):345–369. doi: 10.1016/0002-9149(79)90327-8. [DOI] [PubMed] [Google Scholar]
  16. Somberg J. C., Barry W. H., Smith T. W. Differing sensitivities of Purkinje fibers and myocardium to inhibition of monovalent cation transport by digitalis. J Clin Invest. 1981 Jan;67(1):116–123. doi: 10.1172/JCI110003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sweadner K. J. Isozymes of the Na+/K+-ATPase. Biochim Biophys Acta. 1989 May 9;988(2):185–220. doi: 10.1016/0304-4157(89)90019-1. [DOI] [PubMed] [Google Scholar]
  18. Urayama O., Shutt H., Sweadner K. J. Identification of three isozyme proteins of the catalytic subunit of the Na,K-ATPase in rat brain. J Biol Chem. 1989 May 15;264(14):8271–8280. [PubMed] [Google Scholar]
  19. Wilcox J. N., Smith K. M., Williams L. T., Schwartz S. M., Gordon D. Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization. J Clin Invest. 1988 Sep;82(3):1134–1143. doi: 10.1172/JCI113671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. de MELLO W., HOFFMAN B. F. Potassium ions and electrical activity of specialized cardiac fibers. Am J Physiol. 1960 Dec;199:1125–1130. doi: 10.1152/ajplegacy.1960.199.6.1125. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES