TY - JOUR
T1 - Glucocorticoids stimulate the activity of large-conductance Ca 2+-activated K+ channels in pituitary GH3 and AtT-20 cells via a non-genomic mechanism
AU - Huang, Mei Han
AU - So, Edmund Cheung
AU - Liu, Yen Chin
AU - Wu, Sheng Nan
N1 - Funding Information:
This work was aided by grants from National Science Council (NSC-92-2320B-006-041 and NSC-93-2320B-006-055), Taiwan.
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.steroids.2005.09.009
DO - 10.1016/j.steroids.2005.09.009
M3 - Article
C2 - 16274717
AN - SCOPUS:30644459980
SN - 0039-128X
VL - 71
SP - 129
EP - 140
JO - Steroids
JF - Steroids
IS - 2
ER -