REVIEW article
Front. Physiol.
Sec. Integrative Physiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1694027
This article is part of the Research TopicThe Sodium Pump and Cardiotonic Steroids in Health and DiseaseView all 7 articles
Na,K-ATPase mediated and cardiotonic induced signaling in health and disease
Provisionally accepted
- The University of Kansas Department of Cell Biology & Physiology, Kansas City, United States
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In the late 1950's, Na,K-ATPase (NKA) was discovered as the active transport system that establishes and maintains the transmembrane Na+ and K+ gradients necessary for cell survival and function. Almost 70 years later, a novel unexpected function for NKA was unveiled, when it was shown that NKA has the amazing versatility of playing a role beyond its classical "ion pumping" function to also serve as the receptor and signal transducer for the effects of cardiotonic steroids (CTS) in cells. Since then, the field of NKA research expanded into a new dimension. The additional unexpected finding that CTS are commonly present in the body fluids of mammals inspired investigators to further study the CTS-induced and NKA-mediated pathway, its mechanisms of action, effects in cells, and importance to tissue and body physiology. Therefore, a vast amount of information has accumulated in recent years. In this article, we attempt to review the most current information available, focusing on the effects of CTS and NKA signaling in physiological and pathological states. We also discuss controversies, unsolved issues, and future directions of this fascinating area of research.
Keywords: Na,K-ATPase isoforms, Cardiotonic steroid, cardenolide, bufadienolide, Ouabain, Intracellular signaling
Received: 27 Aug 2025; Accepted: 07 Oct 2025.
Copyright: © 2025 Blanco, Trant, Lowery and Morales-Sosa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Gustavo Blanco, gblanco@kumc.edu
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