Estradiol rapidly induces the translocation and activation of the intermediate conductance calcium activated potassium channel in human eccrine sweat gland cells.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Muchekehu
Ruth W
RW
Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, P.O. Box 9063, Dublin 9, Ireland. rmuchekehu@ucsd.edu
Harvey
Brian J
BJ
D002147:Calmodulin / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004439:Eccrine Glands / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D002147:Calmodulin; D024681:Potassium Channels, Calcium-Activated; D011960:Receptors, Estrogen; D014443:Tyrosine; D004958:Estradiol