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Sodium/Potassium Homeostasis in the Cell

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Metallomics and the Cell

Part of the book series: Metal Ions in Life Sciences ((MILS,volume 12))

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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