Abstract
Na,K-ATPase is a protein ubiquitously expressed in the plasma membrane of all animal cells and vitally essential for their functions. A specialized functional diversity of the Na,K-ATPase isozymes is provided by molecular heterogeneity, distinct subcellular localizations, and functional interactions with molecular environment. Studies over the last decades clearly demonstrated complex and isoform-specific reciprocal functional interactions between the Na,K-ATPase and neighboring proteins and lipids. These interactions are enabled by a spatially restricted ion homeostasis, direct protein-protein/lipid interactions, and protein kinase signaling pathways. In addition to its “classical” function in ion translocation, the Na,K-ATPase is now considered as one of the most important signaling molecules in neuronal, epithelial, skeletal, cardiac and vascular tissues. Accordingly, the Na,K-ATPase forms specialized sub-cellular multimolecular microdomains which act as receptors to circulating endogenous cardiotonic steroids (CTS) triggering a number of signaling pathways. Changes in these endogenous cardiotonic steroid levels and initiated signaling responses have significant adaptive values for tissues and whole organisms under numerous physiological and pathophysiological conditions. This review discusses recent progress in the studies of functional interactions between the Na,K-ATPase and molecular microenvironment, the Na,K-ATPase-dependent signaling pathways and their significance for diversity of cell function.
Highlights
The Na,K-ATPase is “an enzyme of life” because of its essential role in cell life and death
The present review focuses on the isoform-specific functions of the Na,K-ATPase and specialized interactions with molecular environment which underlie a variety of the Na,K-ATPase-dependent regulatory mechanisms
It has been suggested that the Na,K-ATPase functions as a tetraprotomer (Hah et al, 1985) where single cardiotonic steroids (CTS) blocks all pumping activity but digoxin-like steroids are able to reactivate the ouabain-inhibited tetraprotomers via de-oligomerization (Song et al, 2014)
Summary
The Na,K-ATPase is “an enzyme of life” because of its essential role in cell life and death. Stimulation with agonists was, less effective in the α2-isozyme-downregulated arteries where both sensitization to Ca2+ and Ca2+ release through the IP3 receptors were suppressed The reason for this compromised agonist-induced Ca2+ sensitivity in the arteries with reduced α2 Na,K-ATPase isozyme expression is not known but it suggests a more complex mechanism for the control of smooth muscle contractility by the Na,K-ATPase than the modulation of intracellular Ca2+ concentration via membrane potential (Mulvany et al, 1984; Aalkjaer and Mulvany, 1985) and ion homeostasis (Golovina et al, 2003; Lynch et al, 2008). It has been suggested that the Na,K-ATPase functions as a tetraprotomer (Hah et al, 1985) where single CTS blocks all pumping activity but digoxin-like steroids are able to reactivate the ouabain-inhibited tetraprotomers via de-oligomerization (Song et al, 2014) This antagonism is shown for resistance arteries in vitro. The participation of dystrophin and other potential molecular partners, such as spectrins and ankyrins (Williams et al, 2001; Lencesova et al, 2004; Mohler et al, 2005; Doi and Iwasaki, 2008) in the formation of the nAChR/α2 Na,K-ATPase complex remains to be elucidated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
