Document Detail

Contribution of KCNQ1 to the regulatory volume decrease in the human mammary epithelial cell line MCF-7.
MedLine Citation:
PMID:  17596298     Owner:  NLM     Status:  MEDLINE    
Using the human mammary epithelial cell line MCF-7, we have investigated volume-activated changes in response to hyposmotic stress. Switching MCF-7 cells from an isosmotic to a hyposmotic solution resulted in an initial cell swelling response, followed by a regulatory volume decrease (RVD). This RVD response was inhibited by the nonselective K(+) channel inhibitors Ba(2+), quinine, and tetraethylammonium chloride, implicating K(+) channel activity in this volume-regulatory mechanism. Additional studies using chromonol 293B and XE991 as inhibitors of the KCNQ1 K(+) channel, and also a dominant-negative NH(2)-terminal truncated KCNQ1 isoform, showed complete abolition of the RVD response, suggesting that KCNQ1 plays an important role in regulation of cell volume in MCF-7 cells. We additionally confirmed that KCNQ1 mRNA and protein is expressed in MCF-7 cells, and that, when these cells are cultured as a polarized monolayer, KCNQ1 is located exclusively at the apical membrane. Whole cell patch-clamp recordings from MCF-7 cells revealed a small 293B-sensitive current under hyposmotic, but not isosmotic conditions, while recordings from mammalian cells heterologously expressing KCNQ1 alone or KCNQ1 with the accessory subunit KCNE3 reveal a volume-sensitive K(+) current, inhibited by 293B. These data suggest that KCNQ1 may play important physiological roles in the mammary epithelium, regulating cell volume and potentially mediating transepithelial K(+) secretion.
Brenna L vanTol; Sergey Missan; Julie Crack; Shasta Moser; William H Baldridge; Paul Linsdell; Elizabeth A Cowley
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-27
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  293     ISSN:  0363-6143     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-12     Completed Date:  2007-10-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C1010-9     Citation Subset:  IM    
Dept. of Physiology and Biophysics, Dalhousie Univ., Halifax, Nova Scotia B3H 1X5, Canada.
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MeSH Terms
Breast Neoplasms
Cell Line, Tumor
Cell Polarity / physiology
Epithelial Cells / cytology,  physiology*
Extracellular Fluid / metabolism
Hypotonic Solutions / pharmacology
Isotonic Solutions / pharmacology
KCNQ1 Potassium Channel / genetics,  metabolism*
Mammary Glands, Human / cytology*
Membrane Potentials / physiology
Mutagenesis, Site-Directed
Osmotic Pressure
Potassium / metabolism
Potassium Channels, Voltage-Gated / genetics,  metabolism
RNA, Messenger / metabolism
Water-Electrolyte Balance / physiology*
Reg. No./Substance:
0/Hypotonic Solutions; 0/Isotonic Solutions; 0/KCNE3 protein, human; 0/KCNQ1 Potassium Channel; 0/KCNQ1 protein, human; 0/Potassium Channels, Voltage-Gated; 0/RNA, Messenger; 7440-09-7/Potassium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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