Energy-dependent cell volume maintenance in UC-11MG human astrocytomas.

Abstract

Swelling of astrocytes in the brain is a major cause of the morbidity and mortality associated with stroke and head trauma. Using a human astrocytoma cell line (UC-11MG) as a model system, we studied cell volume changes caused by ATP depletion under conditions mimicking hypoxia. ATP levels were reduced to less than 10% of control using the metabolic inhibitors KCN or antimycin in combination with glucose deprivation. This was sufficient to eliminate ouabain-sensitive 86Rb+ uptake, indicating the Na+-K+-adenosinetriphosphatase was not operating. Furosemide-sensitive 86Rb+ uptake was reduced by approximately 60%, indicating Na+-K+-2Cl- cotransport was also sensitive to ATP loss. ATP depletion resulted in a 30-40% reduction of cell volume within 60 min. ATP depletion also resulted in a net loss of intracellular K+. This loss of K+ could be blocked by Ba2+, indicating the K+ loss was through a conductive channel. When the net K+ loss was blocked by Ba2+, the volume decrease was also prevented. The cells remained viable throughout the time period as judged by exclusion of ethidium bromide by 99% of the cells and recovery of ATP levels to 75% of control within 60 min. We conclude that ATP depletion, following inhibition of glycolysis and oxidative phosphorylation, causes astrocytes to shrink because of a more rapid loss of K+ than uptake of Na+. Thus it appears that ATP depletion alone is not sufficient to account for the rapid phase of astrocytic swelling observed during cerebral ischemia.

Statistics

050010001500'93'96'99'02'05'08'11'14'17
Citations per Year

528 Citations

Semantic Scholar estimates that this publication has 528 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Lomneth1989EnergydependentCV, title={Energy-dependent cell volume maintenance in UC-11MG human astrocytomas.}, author={R Lomneth and E. I. Gruenstein}, journal={The American journal of physiology}, year={1989}, volume={257 4 Pt 1}, pages={C817-24} }