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 2+ 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 2+ signalling in the brain. One, Na + /K + ‐ATPase impairment causing illness and neuronal death due to Ca 2+ 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