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P2C-Type ATPases and Their Regulation

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Abstract

P2C-type ATPases are a subfamily of P-type ATPases comprising Na+/K+-ATPase and H+/K+-ATPase. Na+/K+-ATPase is ubiquitously expressed and has been implicated in several neurological diseases, whereas H+/K+-ATPase is found principally in the colon, stomach, and kidney. Both ATPases have two subunits, α and β, but Na+/K+-ATPase also has a regulatory subunit called FXYD, which has an important role in cancer. The most important functions of these ATPases are homeostasis, potassium regulation, and maintaining a gradient in different cell types, like epithelial cells. Na+/K+-ATPase has become a center of attention ever since it was proposed that it might play a crucial role in neurological disorders such as bipolar disorder, mania, depression, familial hemiplegic migraine, rapid-onset dystonia parkinsonism, chronic stress, epileptogenesis, and Alzheimer’s disease. On the other hand, it has been reported that lithium could have a neuroprotective effect against ouabain, which is the best known Na+/K+-ATPase inhibitor, but and high concentrations of lithium could affect negatively H+/K+-ATPase activity, that has a key role in regulating acidosis and potassium deficiencies. Finally, potassium homeostasis regulation is composed of two main mechanisms, extrarenal and renal. Extrarenal mechanism controls plasma levels, shifting potassium from the extracellular to the intracellular, whereas renal mechanism concerns with body balance and is influenced by potassium intake and its urinary excretion. In this article, we discuss the functions, isoforms, and localization of P2C-type ATPases, describe some of their modulators, and discuss their implications in some diseases.

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Acknowledgments

This work was supported by grants from the Basal Center of Excellence in Aging and Regeneration (CONICYT-PFB 12/2007) to NCI and CV, FONDECYT No. 1120156 to NCI and FONDECYT No. 1130741. Rocío Retamales-Ortega was a SQM associate researcher.

We thank the Sociedad Química y Minera de Chile (SQM) for grants on the “Role of Potassium in Hypertension and Cognition” and on “The Effect of Lithium on Human Health” to the CARE Biomedical Center.

Graphic work was carried out using Graphique-Science (http://graphiquescience.blogspot.com). We thank Felipe Serrano for his help with the drawing of our figures.

Conflict of interest

The authors report no conflicts of interest.

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Authors and Affiliations

  1. Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Santiago, Chile

    Rocío Retamales-Ortega, Carlos P. Vio & Nibaldo C. Inestrosa

  2. Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile

    Carlos P. Vio

  3. Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia

    Nibaldo C. Inestrosa

  4. Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile

    Carlos P. Vio & Nibaldo C. Inestrosa

  5. Centro UC Síndrome de Down, Pontificia Universidad Católica de Chile, Santiago, Chile

    Nibaldo C. Inestrosa

  6. CARE Biomedical Center, Faculty of Biological Sciences, P. Catholic University of Chile, Alameda 340, PO Box 114-D, Santiago, Chile

    Nibaldo C. Inestrosa

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  1. Rocío Retamales-Ortega
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  2. Carlos P. Vio
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  3. Nibaldo C. Inestrosa
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Correspondence to Nibaldo C. Inestrosa.

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Retamales-Ortega, R., Vio, C.P. & Inestrosa, N.C. P2C-Type ATPases and Their Regulation. Mol Neurobiol 53, 1343–1354 (2016). https://doi.org/10.1007/s12035-014-9076-z

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