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

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 Ca 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 Ca signalling in the brain. One, Na /K -ATPase impairment causing illness and neuronal death due to Ca 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.