Sodium/Potassium Homeostasis in the Cell

  • Michael Jakob Voldsgaard Clausen
  • Hanne PoulsenEmail author
Part of the Metal Ions in Life Sciences book series (MILS, volume 12)


All animals are characterized by steep gradients of Na+ and K+ across the plasma membrane, and in spite of their highly similar chemical properties, the ions can be distinguished by numerous channels and transporters. The gradients are generated by the Na+,K+-ATPase, or sodium pump, which pumps out Na+ and takes up K+ at the expense of the chemical energy from ATP. Because the membrane is more permeable to K+ than to Na+, the uneven ion distribution causes a transmembrane voltage difference, and this membrane potential forms the basis for the action potential and for much of the neuronal signaling in general. The potential energy stored in the concentration gradients is also used to drive a large number of the secondary transporters responsible for transmembrane carriage of solutes ranging from sugars, amino acids, and neurotransmitters to inorganic ions such as chloride, inorganic phosphate, and bicarbonate. Furthermore, Na+ and K+ themselves are important enzymatic cofactors that typically lower the energy barrier of substrate binding.

In this chapter, we describe the roles of Na+ and K+ in the animal cell with emphasis on the creation and usage of the steep gradients across the membrane. More than 50 years of Na+,K+-ATPase research has revealed many details of the molecular machinery and offered insights into how the pump is regulated by post-translational modifications and specific drugs.


action potential ion gradients membrane potential Na+ and K+ homeostasis ouabain palytoxin renal tubular system secondary transporters sodium pump voltage-gated channels Please cite as: Met. Ions Life Sci. 12 (2013) 41–67 



actuator domain


adenosine 5’-diphosphate


2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid


adenosine 5’-triphosphate


cation-chloride co-transporters


central nervous system


excitatory amino acid transporters


endoplasmic reticulum


familial hemeplegic migraine 2


γ-aminobutyric acid


glucose transporters


K+-coupled Cl exporters


voltage-gated K+ channels


lethal dose, 50%


leucine transporter


nicotinic acetylcholine receptor


Na+-coupled Pi symporter


voltage-gated Na+ channels


subfamily of voltage-gated sodium channels (formerly Nav2.1 in humans)


sodium-coupled bicarbonate transporters


Na+-coupled Cl importers


nucleotide-binding domain


Na+-coupled H+ exporters


Na+-coupled K+ and Cl importers


neurotransmitter sodium symporters


phosphorylation domain


inorganic phosphate


protein kinase A


protein kinase C


rapid-onset dystonia parkinsonism


sodium-dependent glucose transporters


selective serotonin re-uptake inhibitors


transmembrane helices



We are grateful to Poul Nissen for advice and support. MJC and HP were funded by the Danish National Research Center PUMPKIN and HP by The Lundbeck Foundation, The Carlsberg Foundation, and L’Oréal/UNESCO.


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© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Michael Jakob Voldsgaard Clausen
    • 1
  • Hanne Poulsen
    • 1
    Email author
  1. 1.Centre for Structural Biology, Department of Molecular Biology and GeneticsUniversity of AarhusAarhus CDenmark

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