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Na+/K+-ATPase: A Perspective

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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

Na+/K+-ATPase (NKA), a transmembrane protein, facilitates active transport of three Na+ out of the cell and two K+ into the cell with the expense of an ATP. It plays an important role in regulating the ionic homeostasis and maintaining membrane potential. Additionally, NKA plays a crucial role in driving a variety of secondary transport processes such as Na+-dependent glucose and amino acid transport.

NKA is composed of α and β subunits, which have several tissue-specific isoforms. The α subunit of NKA possesses catalytic activity of the enzyme and that contains binding sites for cardiac glycosides, ions, and ATP and also phosphorylation sites for protein kinase A and protein kinase C. The β-subunit is required for the insertion for the catalytic subunit into the membrane and also facilitates cell adhesion and associated signal transduction.

Cardiotonic steroids, for example, ouabain, elicit their effects by inhibiting the NKA activity, thereby raising [Na+]i leading to an increase in [Ca2+]i mainly via NCX, thereby modulating ion concentrations and contractility. There are several synthetic and endogenous protein inhibitors of NKA having similar effects that mediate an increase in [Ca2+]i.

Activation of PKA and PKC by different stimulants, for example, thrombin, regulates NKA activity in pulmonary smooth muscle cell membrane. Regulation of NKA activity by PKA and PKC has been shown to occur upon phosphorylation of FXYD proteins, which are regulated in a tissue-specific manner. Additionally, some hormones, for instance, catecholamines, increase lung fluid clearance via β-adrenergic mediated mechanisms of active Na+ transport across lung epithelial cells. NKA is associated with several cellular functions such as apoptosis and cellular proliferation. Dysregualtion of NKA is implicated for several metabolic and neuronal disorders.

“Looking for the answer:You hunt it,You catch it,You fool yourself,The answer,is always,a step ahead”.

Jens C Skou

Nobel Prize winner in Chemistry (1997)

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Acknowledgement

Financial assistance from the Council of Scientific and Industrial Research, New Delhi, and the DST-Purse Programme of the University of Kalyani is greatly acknowledged.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, 741235, West Bengal, India

    Sajal Chakraborti, Sayed Modinur Rahaman, Md Nur Alam & Tapati Chakraborti

  2. Department of Physiology, University of Arizona, Tucson, AZ, USA

    Amritlal Mandal

  3. Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA, USA

    Biswarup Ghosh

  4. Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel

    Kuntal Dey

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  1. Sajal Chakraborti
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Correspondence to Sajal Chakraborti .

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  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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Chakraborti, S. et al. (2016). Na+/K+-ATPase: A Perspective. 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_1

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