Abstract
The existence of isoforms of Na,K-ATPase suggests the potential for isoform specific function, distribution or regulation. Under the distribution category is the potential for tissue specific expression as well as subcellular compartment specific isoform expression. Under the regulation category is the potential for isoform specific acute regulation of existing pumps as well as chronic regulation of the pool size of isofoms. The picture is further complicated by the fact that there are isoforms of not only the α catalytic subunit but also the ß glycoprotein subunit that make up the heterodimeric sodium pump. Skeletal muscles express the fairly ubiquitous α1 and ß1 subunits as well as the more restricted α2 and ß2 subunits. Cardiac muscles express these subunits (ß2 only reported at mRNA to our knowledge) as well as α3 (24). Thus, there is the potential for four and six different heterodimers to be expressed in skeletal and cardiac muscle, respectively, and the potential for each having a unique function, pattern of subcellular distribution and/or regulation, as summarized in the compartmental model in Figure 1.
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References
Azuma, K.K., Hensley, C.B., Putnam, D.S., and McDonough, A.A. (1991) Hypokalemia decreases Na,K-ATPase α2 but not α1 isoform abundance in heart, muscle and brain. Am. J. Physiol.: Cell Physiol. 260: C958–C964
Azuma, K.K., Hensley, C.B., Tang, M.J., McDonough, A.A. (1993) Thyroid hormone specifically regulates skeletal muscle Na,K-ATPase α2 and ß2 isoforms. Am. J. Physiol. 265:, in press.
Berger, H.J., Werdan, K., and Erdmann E. (1988) Regulation of cardiac glycoside receptors with different affinities for cardiac glycosides in cultured rat heart cells. In: The Na+, K+-pump, Part B: Celluar Aspects. (Alan R. Liss, Inc., 1988), p. 345–352
Bers, D.M., Lederer, W.J., and Berlin, J.R. (1990) Intracellular Ca transients in rat cardiac myocytes: role of Na-Ca exchange in excitation-contraction coupling. Am J Physiol 258: C944–C954
Clausen, T. (1990) Significance of Na,K-ATPase pump regulation in skeletal muscle. NIPS 5: 148–151
Clausen, T. and Everts, M.E. (1989) Regulation of the Na,K-pump in skeletal muscle. Kidney Int’l 35: 1–13
De Pover, A, and Godfraind, T. (1979) Interaction of ouabain with (Na++K+)ATPase from human heart and from guinea-pig heart. Biochem Pharmac 28: 3051–3056
Desilets, M. and Baumgarten, C.M. (1986) Isoproterenol directly stimulates the Na-K pump in isolated cardiac myocytes. Am. J. Physiol. 251, H218–H225
Eisner, D.A. (1990) The Wellcome Prize Lecture: Intracellular Sodium in Cardiac Muscle-Effects on Contraction. Experimental Physiology 75, 437–457
Ferguson, D.W., Berg. W.J., Sanders, J.S., Roach P.J., Kempf, J.S., and Kienzle, M.G. (1989) Sympathoinhibitory Responses to digitalis glycosides in heart failure patients. Circulation 80: 65–77
Frank, J.S., Mottino. G., Reid, D., Molday, R.S. and K.D. Philipson. (1992) Distribution of the Na+-Ca+2 exchange protein in mammalian cardiac myocytes: An immunofluorescence and Immunocolloidal gold-labeling study. J. Cell Biol. 117: 337–345
Grupp, I., Im, WTC, Lee, Co.O, Lee, SW, Pecker, M.S., and Schwartz, A. (1985) Relation of sodium pump inhibition to positive inotropy at low concentrations of ouabain in rat heart muscle. J Physiol 360: 149–160
Hensley, C.B., Tang, M.J., Azuma, K., K. and McDonough, A.A. (1992) Thyroid hormone induction of rat myocardial Na,K-ATPase: Relationship between al, α2 and ß1 mRNA and protein levels at steady state. Am. J. Physiol. 262: C484–C492
Hensley, C.B., Bersohn, M.M., Sarma, J.S.M. Singh, B.N. and A.A. McDonough. Amiodarone decreases Na,K-ATPase α2 and ß2 expression specifically in cardiac ventricle. J. Cell Mol Cardiol. in press.
Higham, S.C, Melikian, J., Karin, N.J., Ismail-Beigi, and Pressley, T.A. Na,K-ATPase expression in C2C12 cells during myogenesis: minimal contribution of α2 isoform to Na,K transport. J. Memb. Biol. 131: 129–136
Horowitz, B. Hensley, C.B., Quintero, M., Azuma, K.K., Putnam, D. and McDonough, A.A. (1990) Differential regulation of Na,K-ATPase α1, α2 and ß subunit mRNA levels by thyroid hormone. J. Biol. Chem. 265:14308–14314
Hundal, H.S., Marette, A., Mitsumoto, Y., Ramlal, T., Blostein, R., and Klip, A. (1992) Insulin indices translocation of the α2 and ß1 subunits of the Na,K-ATPase from intracellular compartments to the plasma membrane in mammalian skeletal muscle J. Biol. Chem. 267:5040–5043
Ikeda, U., Hyman, R., Smith, T.W., and Medford R.M. (1991) Aldosterone-mediated regulation of Na, K-ATPase gene expression in adult and neonatal rat cardiocytes. J Biol. Chem 266: 12058–12066
Jewell, E.A. and Lingrel, J.B. (1991) Comparison of the substrate dependence properties of the rat Na, K-ATPase al, α2, and α3 isoforms expressed in HeLa cells. J. Biol. Chem. 266, 16925–16930
Marcus, F.I., L. H. Opie and E.H. Sonnenblick. (1991) Digitalis and Other Inotropes. In: Drugs and the Heart, W.B. Saunders, Philadelphia
McDonough, A.A., Azuma, K.K., Lescale-Matys, L., Tang, M.J., Nakhoul, F., Hensley, C.B. and Komatsu, Y. (1992) Physiologic Rationale for Multiple Sodium Pump Isoforms — Differential Regulation of α1 vs α2 by Ionic Stimuli. In Ion Motive ATPases. Ann. New York Acad. Sci: 671:156–169
McDonough, A.A., Geering, K., and Farley, R.A. (1990) The sodium pump needs its b subunit. FASEB J. 4, 1598–1605
Orlowski, J. and Lingrel, J.B. (1988) Tissue-specific and developmental regulation of rat Na,K-ATPase catalytic a isoform and b subunit mRNAs. J. Biol. Chem. 263, 10436–10442
Shamraj, O.L., Melvin, D., and Lingrel, J.B. (1991) Expression of Na, K-ATPase isoforms in human heart. Biochem Biophys Res Comm 179: 1434–1440
Shyjan, A.W., Gottardi, C, and Levenson, R. (1990) The Na,K-ATPase β2 subunit is expressed in rat brain and copurifies with Na,K-ATPase activity. J.Biol.Chem. 265: 5166–5169
Sweadner, K.J. (1989) Isozymes of the Na/K-ATPase. Biochim. Biophys. Acta 988, 185–220, 1989.
Zahler, R., Brines, M., Kashgarian, M., Benz, E.J., Jr., and Gilmore-Hebert, M. (1992). The cardiac conduction system in the rat expresses the α2 and α3 iso forms of the Na,K-ATPase. Proc. Natl. Acad. Sci. USA 89, 99–103
Zahler, R., Gilmore-Hebert, M., Baldwin, J.C., Franco, K., and Benz, E.J. (1993) Expression of α isoforms of the Na,K-ATPase in human heart Biochim. Biophys. Acta 1149: 189–194
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© 1994 Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt
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McDonough, A.A., Azuma, K.K., Hensley, C.B., Magyar, C.E. (1994). Physiologic Relevance of the α2 Isoform of Na,K-ATPase in Muscle and Heart. In: Bamberg, E., Schoner, W. (eds) The Sodium Pump. Steinkopff. https://doi.org/10.1007/978-3-642-72511-1_29
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DOI: https://doi.org/10.1007/978-3-642-72511-1_29
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