Permeability change in transformed mouse fibroblasts caused by ionophores, and its relationship to membrane permeabilization by exogenous ATP

Ilan Friedberg, Gary A. Weisman, Barun K. De

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Electrogenic ionophores have been found to induce membrane permeabilization in Swiss mouse 3T3 cells that had undergone spontaneous transformation (3T6 cells). Cells attached to plastic dishes were loaded with [3H] uridine, and then the medium was replaced by buffered salt solution at pH 7.8. The enhancement of membrane permeability was assayed by following the efflux of uridine nucleotides, normally impermeant substances. Titration with electrogenic ionophores, such as carbonylcyanide m-chlorophenylhydrazone (CCCP), SF-6847 and gramicidin D, markedly increased the membrane permeability within a very narrow range of ionophore concentration. Nonelectrogenic ionophores, such as monensin and nigericin, did not affect membrane permeability. Measurements of the distribution of the lipophilic cation tetraphenylphosphonium (TPP+) between the cells and their environment implied that the remarkable increase in permeability took place within a narrow range of membrane potential (Δψ). The data could be explaine by a Δψ threshold value, under which aqueous channels are opened in the plasma membrane. The effects exerted by electrogenic ionophores on the plasma membrane were found to be similar to those induced by exogenous ATP. In both cases rapid efflux of K+, influx of Na+ and reduction of Δψ preceded membrane permeabilization to low molecular weight, charged molecules, such as nucleotides. It is suggested that dissipation of Δψ induces conformational alterations in membranal components, and/or topological changes, such as aggregation of protein molecules, to form membranal aqueous channels. Electrogenic ionophores permeabilize both normal (3T3) and transformed (3T6) mouse fibroblasts, whereas ATP effects are specific for transformed cells. Thus, it is postulated that ATP acts via specific sites on the surface of transformed cells.

Original languageEnglish (US)
Pages (from-to)251-259
Number of pages9
JournalThe Journal of Membrane Biology
Volume83
Issue number3
DOIs
StatePublished - Oct 1 1985
Externally publishedYes

Keywords

  • 3T6 cells
  • external ATP
  • ionophores
  • membrane potential
  • permeability
  • tetraphenylphosphonium

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

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