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Estradiol rapidly induces the translocation and activation of the intermediate conductance calcium activated potassium channel in human eccrine sweat gland cells.
Muchekehu, Ruth W Harvey, Brian J
Muchekehu, Ruth W
Harvey, Brian J
Author
Advisors
Editors
Other Contributors
Date
2009-02
Date Submitted
Keywords
Other Subjects
Subject Mesh
Calmodulin
Cell Line
Cell Membrane
Eccrine Glands
Electric Conductivity
Epithelial Cells
Estradiol
Humans
Phosphorylation
Potassium Channels, Calcium-Activated
Protein Transport
Receptors, Estrogen
Time Factors
Tyrosine
Cell Line
Cell Membrane
Eccrine Glands
Electric Conductivity
Epithelial Cells
Estradiol
Humans
Phosphorylation
Potassium Channels, Calcium-Activated
Protein Transport
Receptors, Estrogen
Time Factors
Tyrosine
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
Abstract
Steroid hormones target K+ channels as a means of regulating electrolyte and fluid transport. In this study, ion transporter targets of Estradiol (E2) were investigated in the human eccrine sweat gland cell line NCL-SG3.
Whole cell patch-clamp studies revealed E2 (10 nM) rapidly activates a whole cell K+ conductance, which is abolished by clotrimazole (30 microM), an inhibitor of the intermediate conductance calcium activated K+ channel (IKCa). The estrogen receptor (ER) antagonist ICI 182, 780 had no effect on this E2 activated K+ conductance, suggesting an estrogen receptor independent mechanism of activation. Confocal microscopy studies revealed under basal conditions that the IKCa channel is located within the cell cytoplasm and in the presence of E2, rapidly translocates to both the apical and basolateral membrane. In the presence of E2, tyrosine phosphorylation of calmodulin, which is known to regulate trafficking of the IKCa channel, is increased, and treatment of cells with the calmodulin inhibitor trifluoperazine (TFP) prevents the E2-induced translocation.
Estradiol rapidly regulates a K+ conductance through the IKCa channel in an estrogen receptor independent manner. E2 stimulates the translocation of IKCa to the cell membrane in a calmodulin dependent manner, representing a novel paradigm of estrogen action in sweat gland epithelial cells.
Whole cell patch-clamp studies revealed E2 (10 nM) rapidly activates a whole cell K+ conductance, which is abolished by clotrimazole (30 microM), an inhibitor of the intermediate conductance calcium activated K+ channel (IKCa). The estrogen receptor (ER) antagonist ICI 182, 780 had no effect on this E2 activated K+ conductance, suggesting an estrogen receptor independent mechanism of activation. Confocal microscopy studies revealed under basal conditions that the IKCa channel is located within the cell cytoplasm and in the presence of E2, rapidly translocates to both the apical and basolateral membrane. In the presence of E2, tyrosine phosphorylation of calmodulin, which is known to regulate trafficking of the IKCa channel, is increased, and treatment of cells with the calmodulin inhibitor trifluoperazine (TFP) prevents the E2-induced translocation.
Estradiol rapidly regulates a K+ conductance through the IKCa channel in an estrogen receptor independent manner. E2 stimulates the translocation of IKCa to the cell membrane in a calmodulin dependent manner, representing a novel paradigm of estrogen action in sweat gland epithelial cells.
Language
en
ISSN
0039-128X
eISSN
ISBN
DOI
10.1016/j.steroids.2008.10.013
PMID
19027769