Abstract
Mammalian cells of different species differ in sensitivity to ouabain. This sensitivity is expressed as reduced intracellular K+ content, reduced rates of protein synthesis, and cessation of cell multiplication. Using 86Rb+ as a measure of intracellular K+, we found higher levels of radioactivity in mixtures of ouabain-sensitive and - resistant cells cultured in the presence of ouabain than predicted from pure cultures of the two component cell types. The simplest explanation is that K+ and 86Rb+ are being transferred from ouabain-resistant to ouabain-sensitive cells, enhancing the total intracellular 86Rb+ in the culture. A function, "index of cooperation," expresses this enhancement as a number ranging from 0 to 1, and permits comparisons to be made under various culture conditions and using various cell types. An index of cooperation greater than 0 requires cell contact, since no enhancement occurs when contact between two cell types in the same culture is prevented. The index of cooperation for a number of different cell combinations agrees with other measures of cell-cell interaction associated with gap junctions, such as electrical coupling and metabolic cooperation. Coculture of ouabain-sensitive and ouabain- resistant cells in the presence of ouabain also leads to restoration of the capacity for protein synthesis. Autoradiography shows that this restoration occurs in the sensitive cell type and is dependent upon contact with ouabain-resistant cells. Furthermore, sensitive cells are able to multiply in the presence of ouabain when cocultured with resistant cells. Thus K+, presumably transferred to sensitive cells through gap junctions, is able to counteract the toxic effects of ouabain on intracellular K+ levels and protein synthesis, and to restore growth.
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Selected References
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- Corsaro C. M., Migeon B. R. Quantitation of contact-feeding between somatic cells in culture. Exp Cell Res. 1975 Oct 1;95(1):39–46. doi: 10.1016/0014-4827(75)90606-0. [DOI] [PubMed] [Google Scholar]
- Cox R. P., Krauss M. R., Balis M. E., Dancis J. Metabolic cooperation in cell culture: studies of the mechanisms of cell interaction. J Cell Physiol. 1974 Oct;84(2):237–252. doi: 10.1002/jcp.1040840210. [DOI] [PubMed] [Google Scholar]
- EAGLE H. Nutrition needs of mammalian cells in tissue culture. Science. 1955 Sep 16;122(3168):501–514. doi: 10.1126/science.122.3168.501. [DOI] [PubMed] [Google Scholar]
- Gilula N. B., Reeves O. R., Steinbach A. Metabolic coupling, ionic coupling and cell contacts. Nature. 1972 Feb 4;235(5336):262–265. doi: 10.1038/235262a0. [DOI] [PubMed] [Google Scholar]
- Hooper M. L., Slack C. Metabolic co-operation in HGPRT+ and HGPRT- embryonal carcinoma cells. Dev Biol. 1977 Feb;55(2):271–284. doi: 10.1016/0012-1606(77)90172-5. [DOI] [PubMed] [Google Scholar]
- LUBIN M. INTRACELLULAR POTASSIUM AND CONTROL OF PROTEIN SYNTHESIS. Fed Proc. 1964 Sep-Oct;23:994–1001. [PubMed] [Google Scholar]
- Pitts J. D., Simms J. W. Permeability of junctions between animal cells. Intercellular transfer of nucleotides but not of macromolecules. Exp Cell Res. 1977 Jan;104(1):153–163. doi: 10.1016/0014-4827(77)90078-7. [DOI] [PubMed] [Google Scholar]
- Simpson I., Rose B., Loewenstein W. R. Size limit of molecules permeating the junctional membrane channels. Science. 1977 Jan 21;195(4275):294–296. doi: 10.1126/science.831276. [DOI] [PubMed] [Google Scholar]