Glucocorticoids stimulate the activity of large-conductance Ca 2+-activated K+ channels in pituitary GH3 and AtT-20 cells via a non-genomic mechanism

Mei Han Huang, Edmund Cheung So, Yen Chin Liu, Sheng Nan Wu

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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 μM. Dexamethasone-induced increase in IK(Ca) density was suppressed by paxilline (1 μM), yet not by glibenclamide (10 μM), pandinotoxin-Kα (1 μM) or mifepristone (10 μM). Paxilline is a blocker of large-conductance Ca 2+-activated K+ (BKCa) channels, while glibenclamide and pandinotoxin-Kα 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 μM) 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 μM) also increased BKCa-channel activity. Dexamethasone-mediated stimulation of I K(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.

Original languageEnglish
Pages (from-to)129-140
Number of pages12
JournalSteroids
Volume71
Issue number2
DOIs
Publication statusPublished - 2006 Feb 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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