Document Detail

Upregulation of swelling-activated Cl- channel sensitivity to cell volume by activation of EGF receptors in murine mammary cells.
MedLine Citation:
PMID:  12702740     Owner:  NLM     Status:  MEDLINE    
Whole-cell recordings showed that, in mouse mammary C127 cells transfected with the full genome of the bovine papilloma virus (BPV), a hypotonic challenge induced the activation of outwardly rectifying Cl- currents with a peak amplitude 2.7 times greater than that in control C127 cells. Cell-attached single-channel recordings showed that BPV-induced augmentation of the peak amplitude of the whole-cell current could not chiefly be explained by a small increase (1.2 times) in unitary conductance. There was no difference between control and BPV-transfected cells in the osmotic cell swelling rate, and hence, osmotic water permeability. However, a plot of the whole-cell current density as a function of cell volume, which was measured simultaneously, showed that the BPV-transfected cells had a strikingly greater volume sensitivity than control cells. Since the E5 protein of BPV has been reported to induce constitutive activation of the epidermal growth factor (EGF) receptor and platelet-derived growth factor (PDGF) receptor in a variety of cell lines including C127 cells, effects of the growth factors on volume-sensitive outwardly rectifying (VSOR) Cl- currents were examined in C127 cells. Application of PDGF peptides failed to affect the Cl- currents in control and BPV-transfected cells, although C127 cells are known to endogenously express PDGF receptors. In contrast, EGF peptides significantly increased the VSOR Cl- current in control cells. However, they failed to induce further augmentation of the current in BPV-transfected cells. VSOR Cl- currents were inhibited by tyrphostin B46, an inhibitor of the EGF receptor tyrosine kinase, in both control and BPV-transfected cells. The IC50 value in BPV-transfected cells (12 micro M) was lower than that in control cells (31 micro M). However, the VSOR Cl- currents in both cell types were insensitive to tyrphostin AG1296, an inhibitor of the PDGF receptor tyrosine kinase. The rate of regulatory volume decrease (RVD) was markedly diminished by tyrphostin B46 but not significantly affected by tyrphostin AG1296. We thus conclude that the EGF receptor tyrosine kinase upregulates the activity of the VSOR Cl- channel, mainly by enhancing the volume sensitivity.
Iskandar F Abdullaev; Ravshan Z Sabirov; Yasunobu Okada
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-04-17
Journal Detail:
Title:  The Journal of physiology     Volume:  549     ISSN:  0022-3751     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-16     Completed Date:  2004-02-02     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  749-58     Citation Subset:  IM    
Department of Cell Physiology, National Institute for Physiological Sciences, CREST of Japan Science and Technology Corporation, Okazaki 444-8585, Japan.
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MeSH Terms
Cell Line
Cell Membrane Permeability / physiology
Cell Size / physiology
Chloride Channels / drug effects,  genetics,  physiology*
Cystic Fibrosis Transmembrane Conductance Regulator / biosynthesis,  genetics
Mammary Glands, Animal / cytology*,  drug effects
Membrane Potentials / physiology
Osmotic Pressure
Patch-Clamp Techniques
Receptor, Epidermal Growth Factor / biosynthesis*,  genetics
Up-Regulation / drug effects,  physiology*
Reg. No./Substance:
0/Chloride Channels; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; EC, Epidermal Growth Factor

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

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