Relationship between functional Na+ pumps and mitogenesis in cultured coronary artery smooth muscle cells.
An increase in functional sarcolemmal Na(+)-K(+)-ATPase (Na+ pump) precedes proliferation in vascular smooth muscle cells (VSMCs) seeded in 10% fetal bovine serum (FBS), but its role in mitogenesis is unresolved. Enzymatically dispersed canine coronary artery VSMCs were seeded in FBS and studied through confluence. Before a shift in cell cycle (G1-->S, G2 + M) and appearance of the nonmuscle isoform of myosin (MHCnm), intracellular Na+ content (Na+i) and cell volume (CV) increased (day 0 through day 3). Na+ pump number ([3H]-ouabain binding) increased at day 4 followed by a decrease in Na+i and CV. When Na+ pumps were inhibited by the addition of ouabain to FBS, VSMCs were arrested in G1, and MHCnm was not upregulated. Na+i increased similarly to that in FBS but failed to correct to day 0 levels. Withdrawal of ouabain at day 4 in culture led to an increase in Na+ pump number, a decrease in Na+i, entry of cells into S and G2 + M, and upregulation of MHCnm. These data suggest that Na+i, phenotypic modulation, and entry of cells into the cell cycle are temporally related, with Na+ pump-mediated correction of increased Na+i as a key event in the VSMC mitogenic process.
Feltes
T F
TF
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
Seidel
C L
CL
Dennison
D K
DK
Amick
S
S
Allen
J C
JC
D000818:Animals; D002412:Cations / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism*; D004285:Dogs; D005260:Female; D005434:Flow Cytometry; D008297:Male; D008934:Mitogens / Q000097:blood / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D010042:Ouabain / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology*
D002412:Cations; D008934:Mitogens; D010042:Ouabain; D009218:Myosins; D000254:Sodium-Potassium-Exchanging ATPase