Epidermal growth factor induces electrically silent Na+ influx in human fibroblasts

Addition of epidermal growth factor (EGF) to quiescent confluent cultures of human foreskin fibroblasts causes a rapid, nearly 2-fold stimulation of unidirectional Na+ influx and a doubling of the rate of the Na+,K+ pump, whereas K+ efflux remains unaltered. The diuretic amiloride, an inhibitor of N...

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Bibliographic Details
Published in:The Journal of biological chemistry 1982-07, Vol.257 (14), p.8502-8506
Main Authors: Moolenaar, W H, Yarden, Y, de Laat, S W, Schlessinger, J
Format: Article
Language:English
Subjects:
Amiloride - pharmacology
Biological Transport - drug effects
Cells, Cultured
Epidermal Growth Factor - pharmacology
Fibroblasts - drug effects
Fibroblasts - metabolism
Humans
Infant, Newborn
Kinetics
Male
Potassium - metabolism
Skin - metabolism
Sodium - metabolism
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Summary:Addition of epidermal growth factor (EGF) to quiescent confluent cultures of human foreskin fibroblasts causes a rapid, nearly 2-fold stimulation of unidirectional Na+ influx and a doubling of the rate of the Na+,K+ pump, whereas K+ efflux remains unaltered. The diuretic amiloride, an inhibitor of Na+/H+ exchange, completely blocks EGF-induced Na+ influx, Na+,K+-pump activity, and DNA synthesis without affecting the cellular binding, visible clustering, and internalization of 125I-labeled and fluorescent EGF. In the absence of EGF, the induction of amiloride-sensitive Na+ influx and Na+,K+-pump activity can be mimicked by exposing the cells to weak acids. Neither the rapid stimulation of Na+ influx by EGF nor its inhibition by amiloride is accompanied by a detectable change in membrane potential (mean value of -66 mV), as evidenced by direct intracellular recording. In contrast, a rapid but transient membrane depolarization of about 50 mV, due to an unselective permeability increase, is observed in response to serum-growth factors. These results (i) indicate that EGF rapidly activates an electroneutral, previously inactive Na+ transport system in the plasma membrane of quiescent fibroblasts, and (ii) suggest that EGF-induced Na+ influx occurs in exchange for intracellular protons. The data further imply that early changes in membrane potential are not necessary for the initiation of a mitogenic response.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)34360-6