ArticleThe Journal of biological chemistry2014
Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Mechanism of Rescue of NaInternational journal of molecular sciences · 2026Article
- On the mechanism of hypomagnesemia with treatment-resistant seizures caused by variants of the Na+,K+-ATPase α1 subunit (ATP1A1).The Journal of general physiology · 2026Article
- The Quaternary Structure of the Sodium Pump Regulatory Complex Is Altered by Mutations of a Site Associated with Familial Hemiplegic Migraine.Molecular neurobiology · 2025Article
- ATP1A3 regulates protein synthesis for mitochondrial stability under heat stress.Disease models & mechanisms · 2024Article
- Activation of Piezo1 Increases Na,K-ATPase-Mediated Ion Transport in Mouse Lens.International journal of molecular sciences · 2022Article
- Disease mutations of human α3 NaPNAS nexus · 2022Article
- Deficiency of Thyroid Hormone Reduces Voltage-Gated NaInternational journal of molecular sciences · 2022Article
- Genetically altered animal models for ATP1A3-related disorders.Disease models & mechanisms · 2021Article
- Early role for a NaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Factors in the disease severity of ATP1A3 mutations: Impairment, misfolding, and allele competition.Neurobiology of disease · 2019Article
- Distinct effects of Q925 mutation on intracellular and extracellular NaScientific reports · 2019Article
- Functional consequences of the CAPOS mutation E818K of NaThe Journal of biological chemistry · 2019Article
- Chemical genetic identification of GAK substrates reveals its role in regulating NaLife science alliance · 2018Article
- Regulation of Neuronal Na,K-ATPase by Extracellular Scaffolding Proteins.International journal of molecular sciences · 2018Article
- Differential contributions of CaHippocampus · 2018Article
- Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2.American journal of human genetics · 2018Article
- On the effect of hyperaldosteronism-inducing mutations in Na/K pumps.The Journal of general physiology · 2017Article
- Article
- Arginine substitution of a cysteine in transmembrane helix M8 converts Na+,K+-ATPase to an electroneutral pump similar to H+,K+-ATPase.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Mosaicism in ATP1A3-related disorders: not just a theoretical risk.Neurogenetics · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neurological disorders familial hemiplegic migraine type 2 (FHM2), alternating hemiplegia of childhood (AHC), and rapid-onset dystonia parkinsonism (RDP) are caused by mutations of Na(+),K(+)-ATPase α2 and α3 isoforms, expressed in glial and neuronal cells, respectively. Although these disorders are distinct, they overlap in phenotypical presentation. Two Na(+),K(+)-ATPase mutations, extending the C terminus by either 28 residues ("+28" mutation) or an extra tyrosine ("+Y"), are associated with FHM2 and RDP, respectively. We describe here functional consequences of these and other neurological disease mutations as well as an extension of the C terminus only by a single alanine. The dependence of the mutational effects on the specific α isoform in which the mutation is introduced was furthermore studied. At the cellular level we have characterized the C-terminal extension mutants and other mutants, addressing the question to what extent they cause a change of the intracellular Na(+) and K(+) concentrations ([Na(+)]i and [K(+)]i) in COS cells. C-terminal extension mutants generally showed dramatically reduced Na(+) affinity without disturbance of K(+) binding, as did other RDP mutants. No phosphorylation from ATP was observed for the +28 mutation of α2 despite a high expression level. A significant rise of [Na(+)]i and reduction of [K(+)]i was detected in cells expressing mutants with reduced Na(+) affinity and did not require a concomitant reduction of the maximal catalytic turnover rate or expression level. Moreover, two mutations that increase Na(+) affinity were found to reduce [Na(+)]i. It is concluded that the Na(+) affinity of the Na(+),K(+)-ATPase is an important determinant of [Na(+)]i.
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