The Na,K-ATPase-Dependent Src Kinase Signaling Changes with Mesenteric Artery Diameter

International Journal of Molecular Sciences
Lin ZhangVladimir V Matchkov

Abstract

Inhibition of the Na,K-ATPase by ouabain potentiates vascular tone and agonist-induced contraction. These effects of ouabain varies between different reports. In this study, we assessed whether the pro-contractile effect of ouabain changes with arterial diameter and the molecular mechanism behind it. Rat mesenteric small arteries of different diameters (150⁻350 µm) were studied for noradrenaline-induced changes of isometric force and intracellular Ca2+ in smooth muscle cells. These functional changes were correlated to total Src kinase and Src phosphorylation assessed immunohistochemically. High-affinity ouabain-binding sites were semi-quantified with fluorescent ouabain. We found that potentiation of noradrenaline-sensitivity by ouabain correlates positively with an increase in arterial diameter. This was not due to differences in intracellular Ca2+ responses but due to sensitization of smooth muscle cell contractile machinery to Ca2+. This was associated with ouabain-induced Src activation, which increases with increasing arterial diameter. Total Src expression was similar in arteries of different diameters but the density of high-affinity ouabain binding sites increased with increasing arterial diameters. We suggested that o...Continue Reading

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Citations

Feb 16, 2019·Experimental Physiology·Christian StaehrVladimir V Matchkov
May 6, 2021·Stroke; a Journal of Cerebral Circulation·Halvor Osterby GuldbrandsenVladimir V Matchkov

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Methods Mentioned

BETA
force measurements

Software Mentioned

GraphPad
GraphPad Prism
ImageJ

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