Downregulation of voltage-gated sodium channels by dexamethasone in clonal rat pituitary cells.
The effect of chronic dexamethasone (DEX) treatment (4-5 days) on Na(+) channel expression was examined in a clonal strain of rat pituitary cells secreting growth hormone (GH) and prolactin (GH3 cells). Using whole-cell patch clamp recording, we found that DEX (1 microM) induces an 80% decrease in Na(+) current density. No concomitant changes in current kinetics or voltage dependence of Na(+) channel function were detected. Instead, the decrease in current density was accompanied by a similar reduction in maximal Na(+) conductance, suggesting the loss of Na(+) channels from the plasma membrane. Accordingly, saxitoxin binding assays carried out on intact cells showed that the average number of Na(+) channels per cell is markedly decreased by DEX. Thus, this glucocorticoid inhibits the cell surface expression of Na(+) channels when chronically applied to GH3 cells.
Avila
Guillermo
G
Department of Biochemistry, Cinvestav-IPN, AP 14-740, DF 07000, Mexico City, Mexico.
Monjaraz
Eduardo
E
Espinosa
Juan Luis
JL
Cota
Gabriel
G
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism; D015640:Ion Channel Gating; D018408:Patch-Clamp Techniques; D010903:Pituitary Gland, Anterior / Q000378:metabolism* / Q000473:pathology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D015222:Sodium Channels; D003907:Dexamethasone; D011388:Prolactin; D013006:Growth Hormone