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Na+/K+-ATPase

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Na+/K+-ATPase is an enzyme found in the plasma membrane of cells that catalyzes the hydrolysis of ATP to transport sodium ions out of and potassium ions into the cell, maintaining electrochemical gradients essential for various cellular functions, including nerve impulse transmission and muscle contraction.
lightbulbAbout this topic
Na+/K+-ATPase is an enzyme found in the plasma membrane of cells that catalyzes the hydrolysis of ATP to transport sodium ions out of and potassium ions into the cell, maintaining electrochemical gradients essential for various cellular functions, including nerve impulse transmission and muscle contraction.

Key research themes

1. How do structural and molecular mechanisms govern ion binding, transport, and regulation in Na+/K+-ATPase?

This research area focuses on uncovering the detailed molecular architecture and dynamics of the Na+/K+-ATPase (NKA) protein complex that underlie its ability to selectively bind and transport Na+ and K+ ions. Understanding the protonation states of key residues, isoform-specific ion affinities, conformational changes during ion occlusion and release, and the impact of disease mutations elucidate the enzyme's transport mechanism and regulatory potential. Such insights advance foundational knowledge critical for drug targeting and treatment of related diseases.

Key finding: Using molecular dynamics and density functional theory simulations, the study established that stable Na+ binding in the Na+/K+-ATPase requires specific protonation states, notably protonation of Glu954 in binding site III... Read more
Key finding: By isolating kinetic components of Na+ binding via extracellular Na+-mediated transient currents, this study revealed three distinct kinetic phases (fast, medium, slow) corresponding to ion binding and occlusion events at the... Read more
Key finding: This paper measured the Na+ affinity of Na+/K+-ATPase in native rat skeletal muscle membranes and found higher Na+ affinity in oxidative compared to glycolytic muscle fibers. Isoform composition correlated with these affinity... Read more
Key finding: Through structural and motif analyses, this study identified intrinsic sequence-based endocytic motifs in the α-subunit of Na+/K+-ATPase that regulate pump trafficking between the plasma membrane and intracellular... Read more
Key finding: By systematically mutating 24 residues in transmembrane segment four to cysteine and probing with sulfhydryl reagents, this work mapped accessible residues defining a cation translocation pathway lined by the fourth... Read more

2. How is Na+/K+-ATPase regulated through interaction with signaling molecules, post-translational modifications, and cellular trafficking to control physiological functions?

This theme investigates the multidimensional regulation of Na+/K+-ATPase activity beyond ion transport catalysis, focusing on how its signaling functions are modulated by phosphorylation, carbonylation, redox modifications, complex formation with kinases like c-Src, and trafficking dynamics. Such regulatory processes affect cellular ion homeostasis, sodium reabsorption in renal epithelia, cardiac and skeletal muscle excitability, and pathophysiology in diseases. Understanding these regulatory axes guides strategies for therapeutic intervention targeting NKA in metabolic, cardiovascular, and renal contexts.

Key finding: Mutation of Pro224 (corresponding to Pro222 in pig α1) to alanine in rat α1 eliminated ouabain-induced protein carbonylation but did not affect ouabain-mediated inhibition of Na/K-ATPase activity. Importantly, this mutation... Read more
Key finding: Electrophysiological recordings in rat hippocampal neurons demonstrated that Na+/K+-ATPase transport activity is controlled by a balance between phosphorylation by protein kinases PKG and PKC (which inhibit activity) and... Read more
Key finding: Using Blue Native-PAGE, cysteine-directed crosslinking, and capillary immunoblotting, the study revealed that the Na+/K+-ATPase α1 subunit and c-Src kinase form a direct signaling complex under native cellular conditions.... Read more
Key finding: Mass spectrometry and biochemical assays defined that several cysteine residues in the Na+/K+-ATPase α1 subunit are constitutively modified by glutathionylation, nitrosylation, or oxidation. Enzymatic and chemical reduction... Read more
Key finding: This review synthesized evidence that Na+/K+-ATPase functions as a receptor-mediated signaling platform activated by cardiotonic steroids and reactive oxygen species (ROS). Ouabain binding induces ROS generation, activating... Read more

3. How do tissue-specific isoforms and physiological states modulate Na+/K+-ATPase function and adaptation in muscle and epithelial tissues?

This area examines Na+/K+-ATPase isoform expression patterns, kinetic properties, and regulatory mechanisms in diverse tissues such as skeletal muscle and intestinal epithelium and their adaptations during development, exercise, and aging. Understanding isoform-specific kinetic parameters (like substrate affinities), expression changes during epithelial cell maturation, and regulation by cellular factors (extracellular K+, AMPK, PGC-1α) illuminates isozyme specialization for tissue-specific demands and informs therapeutic strategies for related dysfunctions.

Key finding: Electrophysiological measurements in mouse skeletal muscle fibers showed that the α2 isoform of Na,K-ATPase, localized predominantly to T-tubules, possesses a substrate affinity for extracellular K+ closely tuned to the... Read more
Key finding: Long-term activation of AMPK by repeated AICAR injections decreased PLM protein content but increased its phosphorylation, concomitant with an increased Na+ affinity (reduced Km) of the Na,K-ATPase without alteration of α and... Read more
Key finding: This review identified that rodent skeletal muscle exhibits a decline in Na,K-ATPase content (estimated by [3H]ouabain binding) with aging, particularly after peak values in early life, while in human skeletal muscle, such... Read more

All papers in Na+/K+-ATPase

The successful establishment of a species in a given habitat depends on the ability of each of its developing stages to adapt to the environment. In order to understand this process we have studied the adaptation of a euryhaline fish, the... more
Introduction: Since diabetic cardiomyopathy is associated with metabolic abnormalites and subcellular Ca 2+-handling defects, this study examined the effects of metabolic therapy with propionyl L-carnitine (PPLC) in modifying diabetes... more
The sodium pump or Na,K-ATPase was discovered in 1957. In view of the complexity of the system, its mechanism and roles are still not fully understood. The system is often ignored or confused with channels and other transporters. It is... more
The current study was conducted at agro-eycosystem of Basra province during the period 2013-2014, to evaluate the diversity of spiders community. 24 species, 23 genera belong to 10 families was recorded, the most relative abundance was... more
The aim of this study was to evaluate the effect of Biofield Energy Treated/Blessed Proprietary Test Formulation and Biofield Energy Treatment/Blessing per se on cardiac biomarkers in aorta homogenate on L-NAME and high fat diet... more
In 1997 Jens Christian Skou, Aarhus University, Danemark, won the Nobel Prize for hist work on Na,K-ATPase. Due to reconstitution techniques, consisting in the insertion of purified Na,K-ATPase into artificial membranes, the Na,K-ATPase... more
There is a need to control Spodoptera frugiperda with new pesticides that have unusual modes of action. Spodoptera frugiperda initial larval instars can spin silk threads which would be the target of synthetic... more
Literature on the mechanisms of magnesium transport through fish intestine is scarce. Indirect evidence for a net magnesium transport via the intestinal tract of fish has been established by dietary experiments (e.g. with carp Cyprinus... more
The successful establishment of a species in a given habitat depends on the ability of each of its developing stages to adapt to the environment. In order to understand this process we have studied the adaptation of a euryhaline fish, the... more
The European sea bass, Dicentrarchus labrax, being a member of the family Morenidae is a remarkable euryhaline species capable of tolerating both hypersaline and freshwater (FW) environments (1,2). It has been ... Turk J Vet Anim Sci 26... more
This study investigated the dietary component and morphology of the digestive tract of Anguilla marmorata during its yellow stages (non-migrants). A total of 127 samples, ranging in total length from 17-108 cm and weight from 10-3200 g... more
The successful establishment of a species in a given habitat depends on the ability of each of its developing stages to adapt to the environment. In order to understand this process we have studied the adaptation of a euryhaline fish, the... more
Siberian sturgeon farming is important because it provides an alternative source of caviar and meat, but also for the conservation of the endangered natural stocks. Farmed fish is continuously subjected to stress factors, of which, water... more
The histological structure, histochemical features, and enzymatic activity of the digestive tract of juvenile Pacific seahorse (Hippocampus ingens) are described to provide information during the cultivation of this species. Serial... more
In this study, development of the digestive tract of the Black Sea Trout (Salmo trutta labrax PALLAS, 1811) which is endemic and also endangered species in their natural habitat was identified in early larval stages. For this reason, fish... more
Several aspects of the biology of European eel (Anguilla anguilla) larvae are still unknown; particularly, information about their functional development and feeding is sparse. In the present study, we histologically characterize the... more
Bilal Ahmad Paray, Haniffa M.A, Mehraj Ud Din War, Mohammad K. Al-Sadoon, Yong-Ha Park & Irfan A. Rather Centre for Aquaculture Research and Extension, St. Xavier’s College (Autonomous) Palayamkottai, 627-002, India PG and Research... more
The histological structure, histochemical features, and enzymatic activity of the digestive tract of juvenile Pacific seahorse (Hippocampus ingens) are described to provide information during the cultivation of this species. Serial... more
Acclimation trials of wild and hatchery sea bass (Dicentrarchus labrax) fry at different salinities
This study investigated the dietary component and morphology of the digestive tract of Anguilla marmorata during its yellow stages (non-migrants). A total of 127 samples, ranging in total length from 17-108 cm and weight from 10-3200 g... more
The successful establishment of a species in a given habitat depends on the ability of each of its developing stages to adapt to the environment. In order to understand this process we have studied the adaptation of a euryhaline fish, the... more
The successful establishment of a species in a given habitat depends on the ability of each of its developing stages to adapt to the environment. In order to understand this process we have studied the adaptation of a euryhaline fish, the... more
Acclimation trials of wild and hatchery sea bass (Dicentrarchus labrax) fry at different salinities
Acclimation trials of wild and hatchery sea bass (Dicentrarchus labrax) fry at different salinities
The ontogeny of osmoregulation was examined in the branchial cavity of embryonic and early post-embryonic stages of the crayfish Astacus leptodactylus maintained in freshwater, at the sub-cellular level through the detection of the... more
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly... more
Despite the relevance of primary cell culture from the gill tissue, there are no reports on the branchial cell lines of the striped bass Morone saxatilis (Walbaum, 1792). The importance of establishing cell lines from M. saxatilis... more
The development of osmoregulatory and gas exchange organs was studied in larval yellowfin tuna (Thunnus albacares) from 2 to 25 days post-hatching (2.9-24.5 mm standard length, SL). Cutaneous and branchial ionocytes were identified using... more
This paper discusses current views of ion transport in cardiac cell membrane and how the views have changed from classical membrane models. Data from patch clamp experiments is making it possible to construct state-diagram models for... more
The Na,K-stimulated ATPase is inhibited by extra-cellular cardiac glycosides, which bind to the enzyme's (Y subunit. We used a monoclonal antibody, VG4, as a probe of the extracellular surface. The antibody was specific for Na,K-ATPase... more
lished, though generally poorly accepted, fact for several species of teleost and may make a considerable contribution to the uptake of water in dilute media.
The anatomy and the histology of the digestive tract of young and adult sea-bream is described from studies using light and scanning electron microscopy. The dentition in the juvenile (25-30 mm long) comprises all canine-like teeth. to... more
In this study, development of the digestive tract of the Black Sea Trout (Salmo trutta labrax PALLAS, 1811) which is endemic and also endangered species in their natural habitat was identified in early larval stages. For this reason, fish... more
The digestive tract of Takifugu rubripes during early life stages was studied with light microscopy. At the beginning of hatching, the digestive tract is represented by a simple and undifferentiated straight tube and does not communicate... more
We present here a Hopf bifurcation that has the shape of an « e » (we provide a figure beneath), studied with more details in Dieterlen 1981. The 2 variables are the reaction temperature and delta(x), the difference between outside and... more
The osmoregulatory system of two groups of young Persian sturgeon Acipenser persicus (BORODIN) was studied by means of monitoring changes in blood serum and urine osmolarity level after the transfer of young fish from fresh (Control) to... more
Freshwater acclimatized spotted scat (Scatophagus argus) adults were adapted to 5, 10, 20 or 30 g/l seawater and observed for morphometric changes in gill and kidney histology at time points 1, 2, 10, 15 and 30 days. The overall... more
Glass eels (Anguilla anguillu, L. 1758) caught during ascent at the mouth of the RiverTiber were kept in aquaria with freshwater and full strength salinity (35 %) for four months. Morphological features of glass eels at capture and after... more
The ontogeny of differentiated osmoregulatory epithelia in the branchial chamber (gills, branchiostegite, pleura, epipodite) was studied by transmission electron microscopy throughout the postembryonic development of Penaeus japonicus.... more
by J. Lignot and 
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The localization of Na + ,K + -ATPase in epithelia of the organs of the branchial cavity of Homarus gammarus exposed to seawater and dilute seawater was examined by immunofluorescence microscopy and immunogold electron microscopy with a... more
Atlantic red porgy, Pagrus pagrus, is an important reef fish species in the Mediterranean and the snapper-grouper complex off the southeastern United States. Red porgy is a viable candidate for aquaculture with high market value and the... more
The aim of the study was to give an overview of the mechanism of inhibition of Na+/K+-ATPase and Mg2+-ATPase activity, the enzymes playing a key role in the active transport of monovalent cations (Na+ and K+) across the cell membrane,... more
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