A Hundred Years of Sodium Pumping

Glynn, I. M.

doi:10.1146/annurev.physiol.64.081501.130716

Cited by 79 publications

(49 citation statements)

References 85 publications

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“…The Na-K-ATPase, also known as the sodium-potassium pump, is a transporter protein that is expressed ubiquitously in cell membranes of higher eukaryotes (20,23). It is important for maintaining the Na ϩ gradient, which drives the apical absorption of glucose in SGLT1.…”

Section: Na-k-atpasementioning

confidence: 99%

Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Thorsen

Drengstig

Ruoff

2014

American Journal of Physiology-Cell Physiology

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Thorsen K, Drengstig T, Ruoff P. Transepithelial glucose transport and Na ϩ /K ϩ homeostasis in enterocytes: an integrative model. Am J Physiol Cell Physiol 307: C320 -C337, 2014. First published June 4, 2014; doi:10.1152/ajpcell.00068.2013.-The uptake of glucose and the nutrient coupled transcellular sodium traffic across epithelial cells in the small intestine has been an ongoing topic in physiological research for over half a century. Driving the uptake of nutrients like glucose, enterocytes must have regulatory mechanisms that respond to the considerable changes in the inflow of sodium during absorption. The Na-K-ATPase membrane protein plays a major role in this regulation. We propose the hypothesis that the amount of active Na-K-ATPase in enterocytes is directly regulated by the concentration of intracellular Na ϩ and that this regulation together with a regulation of basolateral K permeability by intracellular ATP gives the enterocyte the ability to maintain ionic Na ϩ /K ϩ homeostasis. To explore these regulatory mechanisms, we present a mathematical model of the sodium coupled uptake of glucose in epithelial enterocytes. Our model integrates knowledge about individual transporter proteins including apical SGLT1, basolateral Na-K-ATPase, and GLUT2, together with diffusion and membrane potentials. The intracellular concentrations of glucose, sodium, potassium, and chloride are modeled by nonlinear differential equations, and molecular flows are calculated based on experimental kinetic data from the literature, including substrate saturation, product inhibition, and modulation by membrane potential. Simulation results of the model without the addition of regulatory mechanisms fit well with published short-term observations, including cell depolarization and increased concentration of intracellular glucose and sodium during increased concentration of luminal glucose/sodium. Adding regulatory mechanisms for regulation of Na-K-ATPase and K permeability to the model show that our hypothesis predicts observed long-term ionic homeostasis.enterocytes; epithelial transport; homeostasis; mathematical modeling; ionic regulation THE UPTAKE AND TRANSPORT OF glucose by the epithelial enterocytes in the small intestine are essential steps in all higher animals. Much of the glucose uptake in the small intestine is coupled to transport of sodium, and the different transporter proteins involved in the sodium coupled glucose uptake are well known (23,61,67,97). Although the electrochemical kinetics of the individual transporter proteins responsible for glucose and nutrient uptake are fairly elucidated (19,54,67,82,97), the combined function in which these transporters drive a net inflow of nutrients from the intestinal lumen to the serosal blood has not yet been modeled in detail.We have developed a mathematical model of an enterocyte that incorporates the available kinetic data from studies on individual transporter proteins. The model includes apical SGLT1 (the glucose sodium cotransporter), coupled apical flow of Na ϩ an...

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Section: Na-k-atpasementioning

confidence: 99%

Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Thorsen

Drengstig

Ruoff

2014

American Journal of Physiology-Cell Physiology

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“…Depending on the specific ionic composition on both sides of the membrane, the pump catalyzes several partial reactions (3). In the absence of K ϩ , NKA mediates ATP-driven Na ϩ transport processes, including exchange as well as uncoupled efflux (reviewed in ref.…”

mentioning

confidence: 99%

Capsazepine, a synthetic vanilloid that converts the Na,K-ATPase to Na-ATPase

Mahmmoud

2008

Proc. Natl. Acad. Sci. U.S.A.

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Capsazepine (CPZ), a synthetic capsaicin analogue, inhibits ATP hydrolysis by Na,K-ATPase in the presence but not in the absence of K ؉ . Studies with purified membranes revealed that CPZ reduced Na ؉ -dependent phosphorylation by interference with Na ؉ binding from the intracellular side of the membrane. Kinetic analyses showed that CPZ stabilized an enzyme species that constitutively occluded K ؉ . Low-affinity ATP interaction with the enzyme was strongly reduced after CPZ treatment; in contrast, indirectly measured interaction with ADP was much increased, which suggests that composite regulatory communication with nucleotides takes place during turnover. Studies with lipid vesicles revealed that CPZ reduced ATP-dependent digitoxigenin-sensitive 22 Na ؉ influx into K ؉ -loaded vesicles only at saturating ATP concentrations. The drug apparently abolishes the regulatory effect of ATP on the pump. Drawing on previous homology modeling studies of Na,K-ATPase to atomic models of sarcoplasmic reticulum Ca-ATPase and on kinetic data, we propose that CPZ uncouples an Na ؉ cycle from an Na ؉ /K ؉ cycle in the pump. The Na ؉ cycle possibly involves transport through the recently characterized Na ؉ -specific site. A shift to such an uncoupled mode is believed to produce pumps mediating uncoupled Na ؉ efflux by modifying the transport stoichiometry of single pump units.sodium pump ͉ uncoupling ͉ potassium occlusion N a,K-ATPase (NKA), a P-type cation pump (1), utilizes energy from ATP hydrolysis to exchange intracellular Na ϩ for extracellular K ϩ against their electrochemical potential gradients. The functional pump contains an ␣-subunit that undergoes substrateinduced conformational transitions, coupling ATP hydrolysis to ion transport, and a ␤-subunit important for maturation and targeting of the complex to the membrane (2).According to the Albers-Post scheme, occlusion of three intracellular Na ϩ ions promotes phosphorylation of the ␣-subunit from ATP, whereas occlusion of two extracellular K ϩ ions promotes dephosphorylation (2). Depending on the specific ionic composition on both sides of the membrane, the pump catalyzes several partial reactions (3). In the absence of K ϩ , NKA mediates ATP-driven Na ϩ transport processes, including exchange as well as uncoupled efflux (reviewed in ref. 4). Furthermore, in inside-out vesicles of human red cells, the ratio of net 22 Na ϩ influx/ 86 Rb ϩ efflux was reduced at sub-millimolar cytoplasmic Na ϩ concentrations. This finding indicates that under this particular condition, the pump can function with less than a maximum number of sites filled with Na ϩ ions (5).In sarcoplasmic reticulum (SR) Ca 2ϩ -ATPase (SERCA), the best characterized P-type pump, ATP hydrolysis can take place without Ca 2ϩ transport to allow for thermogenesis (6). This uncoupling is prominent in the presence of a Ca 2ϩ gradient across the SR membrane. Recent studies have shown that sarcolipin, a small SERCA regulator, increases heat production by this pump (7). This finding demonstrates a regulatory inter...

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“…A detailed description of the overall functioning of the pump, as well as some graphical representations, can be found in [11,12]. Na-K pump is under the control of many regulatory mechanisms and pathways.…”

Section: Sodium-potassium Exchange Pumpmentioning

confidence: 99%

“…For further notions about Na-K pump, the interested reader can consult the reviews [11,12,14,19], or more general books [1,16].…”

Section: Sodium-potassium Exchange Pumpmentioning

confidence: 99%

A P System Description of the Sodium-Potassium Pump

Besozzi

Ciobanu

2005

Membrane Computing

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Abstract. The sodium-potassium pump is a fundamental transmembrane protein present in all animal cells. The functioning of the pump is described and analyzed in the formal framework of P systems, considered here as tools for modelling a bio-cellular process. New features such as variable membrane labelling, activation conditions for rules, membrane bilayer and specific communication rules are defined, to the aim of providing a more appropriate description of the pump. A Sevilla carpet of the sodium-potassium pump is given, as a starting point to identify the pumps as the processors able to execute the rules of a high-level P system in a maximal parallel and nondeterministic manner, activated and controlled by steady-state concentrations. Some related topics for further research are proposed.

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A Hundred Years of Sodium Pumping

Cited by 79 publications

References 85 publications

Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Capsazepine, a synthetic vanilloid that converts the Na,K-ATPase to Na-ATPase

A P System Description of the Sodium-Potassium Pump

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A Hundred Years of Sodium Pumping

Cited by 79 publications

References 85 publications

Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model

Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model

Capsazepine, a synthetic vanilloid that converts the Na,K-ATPase to Na-ATPase

A P System Description of the Sodium-Potassium Pump

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Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model