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

Author(s)

Kinoshita, Paula Fernanda ; Marques Orellana, Ana Maria ; Nakao, Vinicius Watanabe ; de Souza Port's, Natacha Medeiros ; Menezes Quintas, Luis Eduardo ; Kawamoto, Elisa Mitiko ; Scavone, Cristoforo

• Document type: Journal article
• Source: British Journal of Pharmacology; v. 179, n. 8, p. 13-pg., 2021-03-30.

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. (AU)

• FAPESP's process: 16/22996-9 - Evaluation of physical exercise effects on cognition of neuronal-PTEN deleted animals
• Grantee: Elisa Mitiko Kawamoto Iwashe
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/14289-6 - The role of Klotho protein in Alzheimer's disease
• Grantee: Paula Fernanda Kinoshita
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/07427-8 - Aging and neuroprotection: effects of Klotho protein in energetic metabolism, Na,K-ATPase signaling and adaptative response in central nervous system
• Grantee: Cristoforo Scavone
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/12974-6 - Evaluation of PTEN inhibition and compartmentalization effects in the presence of neuroinflammation: participation of glutamatergic signaling
• Grantee: Elisa Mitiko Kawamoto Iwashe
• Support Opportunities: Regular Research Grants