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The Role of the Second Na+ Pump in Mammals and Parasites

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Regulation of Membrane Na+-K+ ATPase

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 15))

Abstract

The mechanism for active (ATP-dependent) Na+ extrusion from intracellular compartments, not coupled to K+ influx and insensitive to ouabain, was discovered 50 years ago by Whittembury using renal cortical tissue, and is commonly denominated “the second Na+ pump.” This Na+-ATPase, sensitive to furosemide and ethacrynic acid, exists in both polarized and non-polarized cells and transports Na+ coupled to Cl− in an electroneutral fashion, so the membrane potential is not changed during Na+ transport cycles. Cloning of the enzyme revealed proteins of 1039 amino acids in Trypanosoma cruzi (TcENA) and 811 amino acids in guinea pig enterocytes (ATNA). They share the main functional catalytic domains, which are highly conserved in the P-type ATPase family, but alignment of the parasite and mammalian enzymes reveals scant homology in terms of residues (Ser and Thr) that are potentially phosphorylatable by protein kinases. These differences in primary sequence indicate that selective regulatory mechanisms of the Na+-ATPases evolved differently to favor adaptation to different environmental challenges (i.e., acquisition of scarce nutrients in parasites). The second pump in mammals (kidney and heart) is regulated by signaling cascades that include angiotensins, angiotensin receptors, protein kinase C, and cyclic AMP-dependent and extracellular-signal-regulated protein kinases. Reactive oxygen species and NO are also important modulators of the Na+-ATPase. The pump is dysregulated, possibly by abnormal phosphorylations, in diseases and syndromes (frequently associated) such as obesity, chronic undernutrition, hypertension, and cardiac conduction remodeling with increased risk of sudden death.

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Acknowledgements

We thank BioMedEs (UK) for correcting the English as required. Data from our laboratories were obtained with financial support from the Brazilian National Research Council (CNPq), the Carlos Chagas Rio de Janeiro State Research Foundation (FAPERJ), the Pernambuco Research State Foundation (FACEPE), the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES), the Ministry of Health/Department of Science and Technology (MS/DECIT) and the National Institutes of Science and Technology (INCT/National Institute of Science and Technology for Structural Biology and Bioimaging).

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Authors and Affiliations

  1. Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-590, Brazil

    Adalberto Vieyra, Paulo A. Silva, Humberto Muzi-Filho & Juliana Dias

  2. National Center of Structural Biology and Bioimaging-CENABIO/UFRJ, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Adalberto Vieyra, Paulo A. Silva, Humberto Muzi-Filho, Claudia F. Dick, André L. Araujo-dos-Santos, Juliana Dias, Leucio D. Vieira-Filho & Ana D. O. Paixão

  3. Health Sciences Center, Grande Rio University, Duque de Caxias, RJ, Brazil

    Adalberto Vieyra & Paulo A. Silva

  4. Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Claudia F. Dick & André L. Araujo-dos-Santos

  5. Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

    Claudia F. Dick & André L. Araujo-dos-Santos

  6. National Institute of Cancer, Rio de Janeiro, RJ, Brazil

    Juliana Dias

  7. Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, PE, Brazil

    Leucio D. Vieira-Filho & Ana D. O. Paixão

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  1. Adalberto Vieyra
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  2. Paulo A. Silva
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  3. Humberto Muzi-Filho
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  8. Ana D. O. Paixão
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Correspondence to Adalberto Vieyra .

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Editors and Affiliations

  1. Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. University of Manitoba, Institute of Cardiovascular Science St. Boniface Hospital Research, Winnipeg, Manitoba, Canada

    Naranjan S Dhalla

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Vieyra, A. et al. (2016). The Role of the Second Na+ Pump in Mammals and Parasites. In: Chakraborti, S., Dhalla, N. (eds) Regulation of Membrane Na+-K+ ATPase. Advances in Biochemistry in Health and Disease, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-319-24750-2_6

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