Journal article
The α2 isoform Na,K-ATPase modulates contraction of rat mesenteric small artery via cSrc-dependent Ca2+ sensitization
Acta Physiologica, Vol.224(1), e13059
2018
Abstract
Aims: The Na,K-ATPase is involved in a large number of regulatory activities including cSrc-dependent signalling. Upon inhibition of the Na,K-ATPase with ouabain, cSrc activation is shown to occur in many cell types. This study tests the hypothesis that acute potentiation of agonist-induced contraction by ouabain is mediated through Na,K-ATPase-cSrc signalling-dependent sensitization of vascular smooth muscle cells to Ca2+. Methods: Agonist-induced rat mesenteric small artery contraction was examined in vitro under isometric conditions and in vivo in anaesthetized rats. Arterial wall tension and [Ca2+]i in vascular smooth muscle cells were measured simultaneously. Changes in cSrc and myosin phosphatase targeting protein 1 (MYPT1) phosphorylation were analysed by Western blot. Protein expression was examined with immunohistochemistry. The α1 and α2 isoforms of the Na,K-ATPase were transiently downregulated by siRNA transfection in vivo. Results: Ten micromolar ouabain, but not digoxin, potentiated contraction to noradrenaline. This effect was not endothelium-dependent. Ouabain sensitized smooth muscle cells to Ca2+, and this was associated with increased phosphorylation of cSrc and MYPT1. Inhibition of tyrosine kinase by genistein, PP2 or pNaKtide abolished the potentiating effect of ouabain on arterial contraction and Ca2+ sensitization. Downregulation of the Na,K-ATPase α2 isoform made arterial contraction insensitive to ouabain and tyrosine kinase inhibition. Conclusion: Data suggest that micromolar ouabain potentiates agonist-induced contraction of rat mesenteric small artery via Na,K-ATPase-dependent cSrc activation, which increases Ca2+ sensitization of vascular smooth muscle cells by MYPT1 phosphorylation. This mechanism may be critical for acute control of vascular tone. © 2018 Scandinavian Physiological Society.
Details
- Title
- The α2 isoform Na,K-ATPase modulates contraction of rat mesenteric small artery via cSrc-dependent Ca2+ sensitization
- Authors
- E V Bouzinova (Author) - Aarhus University, DenmarkL Hangaard (Author) - Aarhus University, DenmarkC Staehr (Author) - Aarhus University, DenmarkA Mazur (Author) - Aarhus University, DenmarkA Ferreira (Author) - Aarhus University, DenmarkA V Chibalin (Author) - Karolinska Institutet, SwedenShaun L Sandow (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and EngineeringZ Xie (Author) - Marshall University, United StatesC Aalkjaer (Author) - Aarhus University, DenmarkV V Matchkov (Corresponding Author) - Aarhus University, Denmark
- Publication details
- Acta Physiologica, Vol.224(1), e13059; 15
- Publisher
- Wiley-Blackwell Publishing Ltd.
- Date published
- 2018
- DOI
- 10.1111/apha.13059
- ISSN
- 1748-1708; 1748-1708
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99451393102621
- Output Type
- Journal article
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