The Na,K-ATPase in vascular smooth muscle cells

Lin Zhang; Christian Staehr; Fanxing Zeng; Elena V Bouzinova; Vladimir V Matchkov

doi:10.1016/bs.ctm.2019.01.007

The Na,K-ATPase in vascular smooth muscle cells

Curr Top Membr. 2019:83:151-175. doi: 10.1016/bs.ctm.2019.01.007. Epub 2019 Mar 1.

Authors

Lin Zhang¹, Christian Staehr², Fanxing Zeng³, Elena V Bouzinova², Vladimir V Matchkov⁴

Affiliations

¹ Department of Biomedicine, Health, Aarhus University, Aarhus, Denmark; Department of Exercise Physiology, Beijing Sport University, Beijing, China.
² Department of Biomedicine, Health, Aarhus University, Aarhus, Denmark.
³ Department of Exercise Physiology, Beijing Sport University, Beijing, China.
⁴ Department of Biomedicine, Health, Aarhus University, Aarhus, Denmark. Electronic address: vvm@biomed.au.dk.

PMID: 31196604
DOI: 10.1016/bs.ctm.2019.01.007

Abstract

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 Ca²⁺ and Ca²⁺ 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 Ca²⁺ 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.

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

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Humans
Muscle, Smooth, Vascular / cytology*
Signal Transduction
Sodium-Potassium-Exchanging ATPase / metabolism*
src-Family Kinases / metabolism

Substances

src-Family Kinases
Sodium-Potassium-Exchanging ATPase