Evidence that a Na+/Ca2+ antiport system regulates murine erythroleukemia cell differentiation

R. L. Smith, I. G. Macara, R. Levenson

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124 Scopus citations


The Na+ and Ca2+ transport properties of cultured murine erythroleukemia (MEL) cells have been investigated. We have previously shown that amiloride prevents dimethyl sulfoxide-induced MEL cell differentiation via inhibition of an essential Ca2+ influx. Here we show that external Na+ inhibits Ca2+ influx and stimulates Ca2+ efflux from uninduced MEL cells. Increasing the internal Na+ concentration by a brief incubation of cells with ouabain stimulates the rate of 45Ca2+ influx. Amiloride (40 μM) completely blocks the external Na+-stimulated 45Ca2+ efflux and external Na+-inhibitable 45Ca2+ influx. The same concentration of amiloride had no significant effect on net Na+ uptake. These results suggest that a significant fraction of Ca2+ flux across the MEL cell plasma membrane occurs via a Na+/Ca2+ antiport system and that amiloride prevents differentiation by blocking Ca2+ influx through this system. The importance of a Na+/Ca2+ antiport system for MEL cell differentiation is supported by the following observation: increasing the cellular Na+ level by a brief treatment with ouabain plus monensin accelerates MEL cell commitment as effectively as adding the Ca2+ ionophore A23187. We suggest that dimethyl sulfoxide induces MEL cell differentiation by inhibiting the Na+ pump and consequently allowing Ca2+ influx through the Na+/Ca2+ antiport.

Original languageEnglish (US)
Pages (from-to)773-780
Number of pages8
JournalJournal of Biological Chemistry
Issue number2
StatePublished - 1982

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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