• Epilepsy research · Dec 2014

    Long-term decrease in Na+,K+-ATPase activity after pilocarpine-induced status epilepticus is associated with nitration of its alpha subunit.

    • Vinícius Rafael Funck, Leandro Rodrigo Ribeiro, Letícia Meier Pereira, Clarissa Vasconcelos de Oliveira, Jéssica Grigoletto, Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, and Mauro Schneider Oliveira.
    • Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil.
    • Epilepsy Res. 2014 Dec 1; 108 (10): 1705-10.

    AbstractTemporal lobe epilepsy (TLE) is the most common type of epilepsy with about one third of TLE patients being refractory to antiepileptic drugs. Knowledge about the mechanisms underlying seizure activity is fundamental to the discovery of new drug targets. Brain Na(+),K(+)-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. In the present study we tested the hypothesis that decreased Na(+),K(+)-ATPase activity is associated with changes in the alpha subunit phosphorylation and/or redox state. Activity of Na(+),K(+)-ATPase decreased in the hippocampus of C57BL/6 mice 60 days after pilocarpine-induced status epilepticus (SE). In addition, the Michaelis-Menten constant for ATP of α2/3 isoforms increased at the same time point. Nitration of the α subunit may underlie decreased Na(+),K(+)-ATPase activity, however no changes in expression or phosphorylation state at Ser(943) were found. Further studies are necessary define the potential of nitrated Na(+),K(+)-ATPase as a new therapeutic target for seizure disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

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