Sodium and potassium regulate endothelial phospholipase C-γ and Bmx.
The amount of Na(+) and K(+) in the diet promotes significant changes in endothelial cell function. In the present study, a series of in vitro and in vivo experiments determined the role of Na(+) and K(+) in the regulation of two pleckstrin homology domain-containing intracellular signaling molecules, phospholipase C (PLC)-γ1 and epithelial and endothelial tyrosine kinase/bone marrow tyrosine kinase on chromosome X (Bmx), and agonist-generated Ca(2+) signaling in the endothelium. Extracellular K(+) concentration regulated the levels of activated PLC-γ1, Bmx, and carbachol-stimulated intracellular Ca(2+) mobilization in human endothelial cells. Additional experiments confirmed that high-conductance Ca(2+)-activated K(+) channels and phosphatidylinositol 3-kinase mediated these effects. The content of Na(+) and K(+) in the diet also regulated Bmx levels in endothelial cells and activated PLC-γ1 levels in rats in vivo. The effects of dietary K(+) on Bmx were more pronounced in rats fed a high-salt diet compared with rats fed a low-salt diet. These experiments elucidated an endothelial cell signaling mechanism regulated by electrolytes, further demonstrating an integral relationship between endothelial cell function and dietary Na(+) and K(+) content.
Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, Center for Free Radical Biology, Center for Aging, and Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama; and.
Wei-Zhong
WZ
Ying
Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, Center for Free Radical Biology, Center for Aging, and Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama; and.
Kristal J
KJ
Aaron
Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, Center for Free Radical Biology, Center for Aging, and Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama; and Department of Veterans Affairs Medical Center, Birmingham, Alabama psanders@uab.edu.
Paul W
PW
Sanders
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004039:Diet, Sodium-Restricted; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*
D012964:Sodium; C492367:BMX protein, human; C492365:Bmx protein, rat; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051966:Phospholipase C gamma; D011188:Potassium; D002118:Calcium
Tec kinase; bone marrow tyrosine kinase; dietary salt; endothelium; phospholipase c-γ; potassium