Abstract
The earliest known ionic event during Friend murine erythroleukemic (MEL) cell differentiation along the erythroid pathway is a 45% drop in intracellular sodium concentration ([Na+]i) due to a decrease in Na+ influx (Lannigan, D. A., and Knauf, P. A. (1985) J. Biol. Chem. 260, 7322-7324). We have analyzed the mechanism of the decreased Na+ influx. The Na+ influx in uninduced cells was insensitive to dimethylamiloride, bumetanide, and diisothiocyanostilbene disulfonate. The intracellular pH (pHi) did not change up to 15 h after dimethyl sulfoxide induction, at which time Na+ influx has decreased by approximately 40%; thus, the decrease in Na+ influx is not coupled to a change in pHi. A substantial amount of the decrease in Na+ influx seems to result from a drop in amino acid-dependent Na+ transport. This reduction in amino acid-dependent Na+ influx reflects a decrease in net Na+ influx rather than solely in Na+/Na+ exchange and can account for an appreciable portion of the reduction in [Na+]i seen during differentiation. The drop in amino acid-dependent Na+ influx could not be explained by membrane depolarization but was correlated with a decrease in protein synthesis. Inhibition of protein synthesis in uninduced cells by cycloheximide also caused a decrease in Na+ influx. We conclude that during differentiation the reduction in protein synthesis decreases amino acid-dependent Na+ influx which in turn causes a drop in [Na+]i leading to a reduction in the Na+/K+ pump rate.
Highlights
The earliest knownionic event during Friend murine a sequential series of changes initiated by the inducer that erythroleukemic (MEL) cell differentiation along the result in commitment
We found that the decrease than solely in Na+/Na+exchange and can account for in ouabain-sensitive Rb+ uptake was paralleled by a drop in an appreciable portion of the reduction in [Na+Iiseen [Na+Ii[11]
We conclude that during differ- differentiation is associated with a decrease in Na+ influx entiation the reduction in protein synthesis decreases [11].In thispaper we analyze the mechanism of the decreased amino acid-dependent Na+ influx which in turn causes Na' influx. a drop in [Na+Iileading to a reduction in the Na+/K+
Summary
0 1986 by The American Society of Biological Chemists, Inc. Vol 261, No 31, Issue of November 5,pp. 14430-14436,1986 Printed in U.S.A. A substantial amountof the decrease in Na+influx seems to result from a drop in amino acid-dependent Na+transport This reduction in amino acid-dependent ouabain-sensitive Rb' uptake occurs approximately 6 h after the addition of inducers [3].This event appearsto be causally related to differentiation because ouabain will act as an inducer ( apoor one) in some MEL cell clones [4]. We conclude that during differ- differentiation is associated with a decrease in Na+ influx entiation the reduction in protein synthesis decreases [11].In thispaper we analyze the mechanism of the decreased amino acid-dependent Na+ influx which in turn causes Na' influx.
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