Glucocorticoids stimulate the activity of large-conductance Ca2+ -activated K+ channels in pituitary GH3 and AtT-20 cells via a non-genomic mechanism.
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.
Huang
Mei-Han
MH
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, No. 1, University Road, Tainan, Taiwan.
So
Edmund Cheung
EC
Liu
Yen-Chin
YC
Wu
Sheng-Nan
SN
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology
D005938:Glucocorticoids; D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; C105110:Pandinus toxin K-alpha; D012604:Scorpion Venoms; D015735:Mifepristone; C048220:paxilline; D003907:Dexamethasone; D005905:Glyburide