Volume-regulated chloride conductance in the LNCaP human prostate cancer cell line
Laboratoire de Physiologie Cellulaire, Institut National de la Santé et de la Recherche Médicale EPI 9938, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France Patch-clamp recordings were used to study ion currents induced by cell swelling caused by hypotonicity in...
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Published in | American Journal of Physiology: Cell Physiology Vol. 279; no. 4; pp. C1144 - C1154 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Physiological Society
01.10.2000
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Subjects | |
Online Access | Get full text |
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Summary: | Laboratoire de Physiologie Cellulaire, Institut National de la
Santé et de la Recherche Médicale EPI 9938, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France
Patch-clamp recordings were used to study ion
currents induced by cell swelling caused by hypotonicity in human
prostate cancer epithelial cells, LNCaP. The reversal potential of the swelling-evoked current suggested that Cl was the primary
charge carrier (termed I Cl,swell ). The
selectivity sequence of the underlying volume-regulated anion channels
(VRACs) for different anions was
Br I > Cl > F > methanesulfonate glutamate, with relative
permeability numbers of 1.26, 1.20, 1.0, 0.77, 0.49, and 0.036, respectively. The current-voltage patterns of the whole cell currents
as well as single-channel currents showed moderate outward
rectification. Unitary VRAC conductance was determined at 9.6 ± 1.8 pS. Conventional Cl channel blockers
5-nitro-2-(3-phenylpropylamino)benzoic acid (100 µM) and DIDS (100 µM) inhibited whole cell I Cl,swell in a voltage-dependent manner, with the block decreasing from 39.6 ± 9.7% and 71.0 ± 11.0% at +50 mV to 26.2 ± 7.2% and
14.5 ± 6.6% at 100 mV, respectively. Verapamil (50 µM), a
standard Ca 2+ antagonist and P-glycoprotein function
inhibitor, depressed the current by a maximum of 15%. Protein tyrosine
kinase inhibitors downregulated I Cl,swell
(genistein with an IC 50 of 2.6 µM and lavendustin A by
60 ± 14% at 1 µM). The protein tyrosine phosphatase inhibitor
sodium orthovanadate (500 µM) stimulated
I Cl,swell by 54 ± 11%. We conclude that
VRACs in human prostate cancer epithelial cells are modulated via
protein tyrosine phosphorylation.
volume-regulated chloride channels; tyrosine kinase; cell
volume
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Y. M. Shuba and N. Prevarskaya contributed
equally to this work. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0363-6143 1522-1563 |
DOI: | 10.1152/ajpcell.2000.279.4.c1144 |