Modification of biophysical properties of lung epithelial Na+ channels by dexamethasone

Academic Article


  • There is considerable interest in identifying the basic mechanisms by which dexamethasone alters ion transport across the adult alveolar epithelium. Herein, we incubated synchronized A549 cells, a human alveolar epithelial cell line, with dexamethasone (1μM) for 24-48 h. When normalized to HPRT (a housekeeping gene), A549 β- and γ-subunit mRNA levels for the human amiloride-sensitive epithelial sodium channel (hENaC), assessed by RT-PCR, increased by 1.6- and 17-fold respectively, compared with control values (P < 0.05). These changes were abolished by actinomycin D, indicating transcriptional regulation. Western blotting studies revealed that dexamethasone also increased expression of β- and γ-hENaC protein levels. In contrast, α-hENaC mRNA increased by onefold (P > 0.05) and α-hENaC protein level was unchanged. Incubation of A549 cells with dexamethasone increased their whole cell amiloride-sensitive sodium currents twofold and decreased the K0.5 for amiloride from 833 ± 69 to 22 ± 5.4 nM (mean ± SE; P < 0.01). Single channel recordings in the cell-attached mode showed that dexamethasone treatment increased single channel open time and open probability threefold and decreased channel conductance from 8.63 ± 0.036 to 4.4 ± 0.027 pS (mean ± SE; P < 0.01). We concluded that dexamethasone modulates the amiloride-sensitive Na+ channels by differentially regulating the expression of β- and γ-subunits at the mRNA and protein levels in the human A549 cell line, with little effect on α-hENaC subunit.
  • Digital Object Identifier (doi)

    Author List

  • Lazrak A; Samanta A; Venetsanou K; Barbry P; Matalon S
  • Volume

  • 279
  • Issue

  • 3 48-3