The Janus face of ouabain in Na+/K+-ATPase and calcium signalling in neurons

Abstract

Na+/K+-ATPase, a transmembrane protein essential for maintaining the electrochemical gradient across the plasma membrane, acts as a receptor for cardiotonic steroids such as ouabain. Cardiotonic steroids binding to Na+/K+-ATPase triggers signalling pathways or inhibits Na+/K+-ATPas activity in a concentration-dependent manner, resulting in a modulation of Ca2+ levels, which are essential for homeostasis in neurons. However, most of the pharmacological strategies for avoiding neuronal death do not target Na+/K+-ATPase activity due to its complexity and the poor understanding of the mechanisms involved in Na+/K+-ATPase modulation. The present review aims to discuss two points regarding the interplay between Na+/K+-ATPase and Ca2+ signalling in the brain. One, Na+/K+-ATPase impairment causing illness and neuronal death due to Ca2+ signalling and two, benefits to the brain by modulating Na+/K+-ATPase activity. These interactions play an essential role in neuronal cell fate determination and are relevant to find new targets for the treatment of neurodegenerative diseases. LINKED ARTICLES: This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc.