Glucocorticoids stimulate the activity of large-conductance Ca2+ -activated K+ channels in pituitary GH3 and AtT-20 cells via a non-genomic mechanism

Steroids. 2006 Feb;71(2):129-40. doi: 10.1016/j.steroids.2005.09.009. Epub 2005 Nov 4.


The effects of glucocorticoids on ion currents were investigated in pituitary GH3 and AtT-20 cells. In whole-cell configuration, dexamethasone, a synthetic glucocorticoid, reversibly increased the density of Ca2+ -activated K+ current (IK(Ca)) with an EC50 value of 21 +/- 5 microM. Dexamethasone-induced increase in IK(Ca) density was suppressed by paxilline (1 microM), yet not by glibenclamide (10 microM), pandinotoxin-Kalpha (1 microM) or mifepristone (10 microM). Paxilline is a blocker of large-conductance Ca2+ -activated K+ (BKCa) channels, while glibenclamide and pandinotoxin-Kalpha are blockers of ATP-sensitive and A-type K+ channels, respectively. Mifepristone can block cytosolic glucocorticoid receptors. In inside-out configuration, the application of dexamethasone (30 microM) into the intracellular surface caused no change in single-channel conductance; however, it did increase BKCa -channel activity. Its effect was associated with a negative shift of the activation curve. However, no Ca2+ -sensitiviy of these channels was altered by dexamethasone. Dexamethasone-stimulated channel activity involves an increase in mean open time and a decrease in mean closed time. Under current-clamp configuration, dexamethasone decreased the firing frequency of action potentials. In pituitary AtT-20 cells, dexamethasone (30 microM) also increased BKCa -channel activity. Dexamethasone-mediated stimulation of IK(Ca) presented here that is likely pharmacological, seems to be not linked to a genomic mechanism. The non-genomic, channel-stimulating properties of dexamethasone may partly contribute to the underlying mechanisms by which glucocorticoids affect neuroendocrine function.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dexamethasone / antagonists & inhibitors
  • Dexamethasone / pharmacology*
  • Glucocorticoids / antagonists & inhibitors
  • Glucocorticoids / pharmacology*
  • Glyburide / pharmacology
  • Indoles / pharmacology
  • Kinetics
  • Large-Conductance Calcium-Activated Potassium Channels / drug effects*
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism
  • Mice
  • Mifepristone / pharmacology
  • Pituitary Gland / cytology
  • Pituitary Gland / drug effects*
  • Pituitary Gland / metabolism
  • Rats
  • Scorpion Venoms / pharmacology


  • Glucocorticoids
  • Indoles
  • Large-Conductance Calcium-Activated Potassium Channels
  • Pandinus toxin K-alpha
  • Scorpion Venoms
  • Mifepristone
  • paxilline
  • Dexamethasone
  • Glyburide