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

Authors:
Antônio M. Rodrigues;Antônio-Carlos G. Almeida;Antonio F. C. Infantosi;Hewerson Z. Teixeira;Mario A. Duarte
Affiliations:
Biomedical Engineering Program, COPPE, Federal University of Rio de Janeiro, Brazil and Laboratory of Experimental and Computational Neuroscience, Biomedical Engineering Department, Federal Univer ...;Laboratory of Experimental and Computational Neuroscience, Biomedical Engineering Department, Federal University of São João del-Rei, São João del-Rei, MG 36.301-160, Brazil;Biomedical Engineering Program, COPPE, Federal University of Rio de Janeiro, Brazil;Laboratory of Experimental and Computational Neuroscience, Biomedical Engineering Department, Federal University of São João del-Rei, São João del-Rei, MG 36.301-160, Brazil;Laboratory of Experimental and Computational Neuroscience, Biomedical Engineering Department, Federal University of São João del-Rei, São João del-Rei, MG 36.301-160, Brazil
Venue:
Computational Biology and Chemistry
Year:
2008

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Research Article: Investigating the potassium interactions with the palytoxin induced channels in Na+/K+ pump

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Palytoxin inhibits the sodium-potassium pump --- an investigation of an electrophysiological model using probabilistic model checking

SBMF'12 Proceedings of the 15th Brazilian conference on Formal Methods: foundations and applications
Probabilistic Model Checking Analysis of Palytoxin Effects on Cell Energy Reactions of the Na+/K+-ATPase

IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB)

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Abstract

The ATP hydrolysis reactions responsible for the Na^+/K^+-ATPase phosphorylation, according to recent experimental evidences, also occur for the PTX-Na^+/K^+ pump complex. Moreover, it has been demonstrated that PTX interferes with the enzymes phosphorylation status. However, the reactions involved in the PTX-Na^+/K^+ pump complex phosphorylation are not very well established yet. This work aims at proposing a reaction model for PTX-Na^+/K^+ pump complex, with similar structure to the Albers-Post model, to contribute to elucidate the PTX effect over Na^+/K^+-ATPase phosphorylation and dephosphorylation. Computational simulations with the proposed model support several hypotheses and also suggest: (i) phosphorylation promotes an increase of the open probability of induced channels; (ii) PTX reduces the Na^+/K^+ pump phosphorylation rate; (iii) PTX may cause conformational changes to substates where the Na^+/K^+-ATPase may not be phosphorylated; (iv) PTX can bind to substates of the two principal states E1 and E2, with highest affinity to phosphorylated enzymes and with ATP bound to its low-affinity sites. The proposed model also allows previewing the behavior of the PTX-pump complex substates for different levels of intracellular ATP concentrations.