Model and simulation of Na+/K+ pump phosphorylation in the presence of palytoxin

Rodrigues, Antônio Márcio; Almeida, Antônio-Carlos G. de; Infantosi, Antonio Fernando Catelli; Teixeira, Hewerson Z.; Duarte, Mario Antônio

doi:10.1016/j.compbiolchem.2007.08.001

Cited by 20 publications

(24 citation statements)

References 26 publications

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“…PLTX-like compounds are largely known for their toxicity. A large number of studies, both in vivo [ 16 , 79 , 80 , 81 ] and in vitro [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ] , have been performed in the last three decades to characterize PLTX toxicity and the relevant mechanism of action [ 25 , 26 , 27 , 33 ]. PLTX is recognized as one of the most toxic non-proteinaceous natural compound known, so far.…”

Section: Discussionmentioning

confidence: 99%

“…Na + /K + ATPase transfers three Na + ions out of the cell in trade for two K + ions, exploiting ATP hydrolysis. PLTX binding to the α-β ATPase heterodimer changes the transmembrane pump into a nonspecific monovalent cation channel, leading to a consistent ionic imbalance at the cellular level [ 25 , 26 ]. The channel formed by PLTX binding seems to be a consequence of ATPase conformational changes leading to a loss of pump gate control and uncoupling of the ion transport.…”

Section: Introductionmentioning

confidence: 99%

“…The channel formed by PLTX binding seems to be a consequence of ATPase conformational changes leading to a loss of pump gate control and uncoupling of the ion transport. In addition, PLTX binding reduces the rate of the pump de-phosphorylation, protracting the channel opening [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Palytoxin-Containing Aquarium Soft Corals as an Emerging Sanitary Problem

et al. 2016

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Palytoxin (PLTX), one the most potent marine toxins, and/or its analogs, have been identified in different marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. Although the main concern for human health is PLTXs entrance in the human food chain, there is growing evidence of adverse effects associated with inhalational, cutaneous, and/or ocular exposure to aquarium soft corals contaminated by PLTXs or aquaria waters. Indeed, the number of case reports describing human poisonings after handling these cnidarians is continuously increasing. In general, the signs and symptoms involve mainly the respiratory (rhinorrhea and coughing), skeletomuscular (myalgia, weakness, spasms), cardiovascular (electrocardiogram alterations), gastrointestinal (nausea), and nervous (paresthesia, ataxia, tremors) systems or apparates. The widespread phenomenon, the entity of the signs and symptoms of poisoning and the lack of control in the trade of corals as aquaria decorative elements led to consider these poisonings an emerging sanitary problem. This review summarizes literature data on human poisonings due to, or ascribed to, PLTX-containing soft corals, focusing on the different PLTX congeners identified in these organisms and their toxic potential.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Palytoxin-Containing Aquarium Soft Corals as an Emerging Sanitary Problem

et al. 2016

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“…The types of nonsynaptic interactions that may be involved in the synchronization include: electrotonic interactions mediated by gap‐junctions (Naus et al, 1991; Perez‐Velasques et al, 1994), changes in extracellular space (Roper et al, 1992), field effects (Jefferys & Haas, 1982; Taylor & Dudek, 1982; Dudek et al, 1986), and extracellular ionic fluctuations (Taylor & Dudek, 1984). However, it is not clear how the initiation, the build up, and the termination of epileptic discharges based on nonsynaptic connections happen.…”

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confidence: 99%

Mechanistic hypotheses for nonsynaptic epileptiform activity induction and its transition from the interictal to ictal state—Computational simulation

Almeida¹,

Rodrigues²,

Scorza³

et al. 2008

Epilepsia

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SUMMARYPurpose: The aim of this work is to study, by means of computational simulations, the induction and sustaining of nonsynaptic epileptiform activity. Methods: The computational model consists of a network of cellular bodies of neurons and glial cells connected to a three-dimensional (3D) network of juxtaposed extracellular compartments. The extracellular electrodiffusion calculation was used to simulate the extracellular potential. Each cellular body was represented in terms of the transmembrane ionic transports (Na + /K + pumps, ionic channels, and cotransport mechanisms), the intercellular electrodiffusion through gap-junctions, and the neuronal interaction by electric field and the variation of cellular volume. Results: The computational model allows simulating the nonsynaptic epileptiform activity and the extracellular potential captured the main feature of the experimental measurements. The simulations of the concomitant ionic fluxes and concentrations can be used to propose the basic mechanisms involved in the induction and sustaining of the activities. Discussion: The simulations suggest: The bursting induction is mediated by the Cl ) Nernst potential overcoming the transmembrane potential in response to the extracellular [K + ] increase. The burst onset is characterized by a critical point defined by the instant when the Na + influx through its permeable ionic channels overcomes the Na + / K + pump electrogenic current. The burst finalization is defined by another critical point, when the electrogenic current of the Na + /K + pump overcomes its influx through the channels.

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“…Using this model, experimental procedures were simulated [6,7] to investigate reactions and substates responsible for increasing the enzyme affinity for PTX and its effects on enzyme phosphorylation [8]. A reaction model was also proposed to investigate the interference of PTX with the pump when the enzyme interacts with Na + and/or K + in the absence of ATP [9].…”

Section: Introductionmentioning

confidence: 99%

Hypothesized diprotomeric enzyme complex supported by stochastic modelling of palytoxin-induced Na/K pump channels

et al. 2018

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The sodium–potassium pump (Na+/K+ pump) is crucial for cell physiology. Despite great advances in the understanding of this ionic pumping system, its mechanism is not completely understood. We propose the use of a statistical model checker to investigate palytoxin (PTX)-induced Na+/K+ pump channels. We modelled a system of reactions representing transitions between the conformational substates of the channel with parameters, concentrations of the substates and reaction rates extracted from simulations reported in the literature, based on electrophysiological recordings in a whole-cell configuration. The model was implemented using the UPPAAL-SMC platform. Comparing simulations and probabilistic queries from stochastic system semantics with experimental data, it was possible to propose additional reactions to reproduce the single-channel dynamic. The probabilistic analyses and simulations suggest that the PTX-induced Na+/K+ pump channel functions as a diprotomeric complex in which protein–protein interactions increase the affinity of the Na+/K+ pump for PTX.

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Model and simulation of Na+/K+ pump phosphorylation in the presence of palytoxin

Cited by 20 publications

References 26 publications

Palytoxin-Containing Aquarium Soft Corals as an Emerging Sanitary Problem

Palytoxin-Containing Aquarium Soft Corals as an Emerging Sanitary Problem

Mechanistic hypotheses for nonsynaptic epileptiform activity induction and its transition from the interictal to ictal state—Computational simulation

Hypothesized diprotomeric enzyme complex supported by stochastic modelling of palytoxin-induced Na/K pump channels

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