Contact-mediated communication of ouabain resistance in mammalian cells in culture

Cheryl M. Corsaro, Barbara R. Migeon

Research output: Contribution to journalArticlepeer-review

Abstract

THE active transport of Na+ and K+ across the plasma membrane, mediated by Na+-K+-ATPase, can be inhibited specifically by the cardiac glycoside ouabain1. Ouabain is toxic to mammalian cells in culture, the degree of sensitivity varying with species 2; however, cells resistant to its cytotoxic effects have been obtained in rodent2-4 and human5,6 cell strains. Ouabain-resistant (ouar) cells are thought to have a mutation affecting the Na+-K+-ATPase so that their enzyme has a lower affinity for ouabain than the enzyme of ouabain-sensitive (oua s) cells. Therefore, ouar cells can actively transport Na+ and K+ at ouabain concentrations that would inhibit ouas cells2,4,5. We have observed that ouas human cells, when cocultured densely with ouar human cells, acquire a functional resistance to ouabain as evidenced by their ability to proliferate in medium containing the drug (unpublished observations). We suspected that ouabain resistance was communicated from ouar to ouas cells and that this transfer was a manifestation of ionic transport through a pathway independent of the Na+-K+-ATPase. There is substantial evidence that a specialised membrane structure, the gap junction, is the ultrastructural pathway for the transfer of ions, metabolites and other small molecules between cells in contact7-9. To determine whether the acquisition of ouabain resistance we observed was mediated through gap junctions, we have compared-for the ability to communicate ouabain resistance-cells which are known to form gap junctions with those that cannot. Our results indicate that ouabain resistance can be communicated from oua r to ouas cells, that the process is contact dependent and that it does not occur in cells unable to form gap junctions.

Original languageEnglish (US)
Pages (from-to)737-739
Number of pages3
JournalNature
Volume268
Issue number5622
DOIs
StatePublished - Dec 1 1977

ASJC Scopus subject areas

  • General

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