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Am J Physiol Cell Physiol 264: C169-C178, 1993;
0363-6143/93 $5.00
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AJP - Cell Physiology, Vol 264, Issue 1 C169-C178, Copyright © 1993 by American Physiological Society

ARTICLES

Relationship between functional Na+ pumps and mitogenesis in cultured coronary artery smooth muscle cells

T. F. Feltes, C. L. Seidel, D. K. Dennison, S. Amick and J. C. Allen
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.

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.


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