Vladimir Matchkov

The Na,K-ATPase in vascular smooth muscle cells

Research output: Contribution to book/anthology/report/proceedingBook chapterResearchpeer-review

The Na,K-ATPase is an enzyme essential for ion homeostasis in all cells. Over the last decades, it has been well-established that in addition to the transport of Na + /K + over the cell membrane, the Na,K-ATPase acts as a receptor transducing humoral signals intracellularly. It has been suggested that ouabain-like compounds serve as endogenous modulators of this Na,K-ATPase signal transduction. The molecular mechanisms underlying Na,K-ATPase signaling are complicated and suggest the confluence of divergent biological pathways. This review discusses recent updates on the Na,K-ATPase signaling pathways characterized or suggested in vascular smooth muscle cells. The conventional view on this signaling is based on a microdomain structure where the Na,K-ATPase controls the Na,Ca-exchanger activity via modulation of intracellular Na + in the spatially restricted submembrane space. This, in turn, affects intracellular Ca 2 + and Ca 2 + load in the sarcoplasmic reticulum leading to modulation of contractility as well as gene expression. An ion-transport-independent signal transduction from the Na,K-ATPase is based on molecular interactions. This was primarily characterized in other cell types but recently also demonstrated in vascular smooth muscles. The downstream signaling from the Na,K-ATPase includes Src and phosphatidylinositol-4,5-bisphosphate 3 kinase signaling pathways and generation of reactive oxygen species. Moreover, in vascular smooth muscle cells the interaction between the Na,K-ATPase and proteins responsible for Ca 2 + homeostasis, e.g., phospholipase C and inositol triphosphate receptors, contributes to an integration of the signaling pathways. Recent update on the Na,K-ATPase dependent intracellular signaling and the significance for physiological functions and pathophysiological changes are discussed in this review.

Original languageEnglish
Title of host publicationMembrane transporters in the pathogenesis of cardiovascular and lung disorders
EditorsSergei N. Orlov
Place of publicationCambridge, MA
PublisherAcademic Press
Publication yearJan 2019
ISBN (print)978-0-12-817764-8
Publication statusPublished - Jan 2019
SeriesCurrent Topics in Membranes

    Research areas

  • Blood pressure, Calcium sensitization, Intercellular coupling, Na,K-ATPase, Scaffolding, Signal transduction, Small artery, Smooth muscle cells, Src kinase

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