Back to Search
Start Over
The α2 isoform Na,K-ATPase modulates contraction of rat mesenteric small artery via cSrc–dependent Ca2+ sensitization
- Source :
- Bouzinova, E, Hangaard, L, Staehr, C, Mazur, A, Chibalin, A V, Sandow, S L, Xie, Z, Aalkjær, C & Matchkov, V 2018, ' The α2 isoform Na,K-ATPase modulates contraction of rat mesenteric small artery via cSrc–dependent Ca2+ sensitization ', Acta Physiologica, vol. 223, pp. e13059 . https://doi.org/10.1111/apha.13059
- Publication Year :
- 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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Contraction (grammar)
Vascular smooth muscle
Physiology
Chemistry
Tyrosine phosphorylation
Ouabain
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
0302 clinical medicine
Endocrinology
Internal medicine
Myosin
medicine
Phosphorylation
Na+/K+-ATPase
Tyrosine kinase
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Bouzinova, E, Hangaard, L, Staehr, C, Mazur, A, Chibalin, A V, Sandow, S L, Xie, Z, Aalkjær, C & Matchkov, V 2018, ' The α2 isoform Na,K-ATPase modulates contraction of rat mesenteric small artery via cSrc–dependent Ca2+ sensitization ', Acta Physiologica, vol. 223, pp. e13059 . https://doi.org/10.1111/apha.13059
- Accession number :
- edsair.doi.dedup.....1f24f2257420998fb941c6a4668adb1f