Abstract
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.
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Abbreviations
- A-domain:
-
actuator domain
- ADP:
-
adenosine 5’-diphosphate
- AMPA:
-
2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid
- ATP:
-
adenosine 5’-triphosphate
- CCCs:
-
cation-chloride co-transporters
- CNS:
-
central nervous system
- EAATs:
-
excitatory amino acid transporters
- ER:
-
endoplasmic reticulum
- FHM2:
-
familial hemeplegic migraine 2
- GABA:
-
γ-aminobutyric acid
- GLUTs:
-
glucose transporters
- KCCs:
-
K+-coupled Cl– exporters
- Kv :
-
voltage-gated K+ channels
- LD50 :
-
lethal dose, 50%
- LeuT:
-
leucine transporter
- nAchR:
-
nicotinic acetylcholine receptor
- NaPi:
-
Na+-coupled Pi symporter
- Nav :
-
voltage-gated Na+ channels
- Nax :
-
subfamily of voltage-gated sodium channels (formerly Nav2.1 in humans)
- NCBTs:
-
sodium-coupled bicarbonate transporters
- NCCs:
-
Na+-coupled Cl– importers
- N-domain:
-
nucleotide-binding domain
- NHEs:
-
Na+-coupled H+ exporters
- NKCCs:
-
Na+-coupled K+ and Cl– importers
- NSSs:
-
neurotransmitter sodium symporters
- P-domain:
-
phosphorylation domain
- Pi :
-
inorganic phosphate
- PKA:
-
protein kinase A
- PKC:
-
protein kinase C
- RDP:
-
rapid-onset dystonia parkinsonism
- SGLTs:
-
sodium-dependent glucose transporters
- SSRIs:
-
selective serotonin re-uptake inhibitors
- TMs:
-
transmembrane helices
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Acknowledgments
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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Clausen, M.J.V., Poulsen, H. (2013). Sodium/Potassium Homeostasis in the Cell. In: Banci, L. (eds) Metallomics and the Cell. Metal Ions in Life Sciences, vol 12. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5561-1_3
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