Direct modulation of volume-regulated anion channels by Ca(2+) chelating agents.
Ca(2+) chelating agents are widely used in biological research for Ca(2+) buffering. Here we report that BAPTA, EDTA and HEDTA produce fast, reversible, voltage-dependent inhibition of swelling-activated Cl(-) current (I(Cl,swell)) in LNCaP prostate cancer epithelial cells that is unrelated to their Ca(2+) binding. BAPTA was the most effective (maximal blockade 67%, IC(50)=70 microM, at +100 mV) followed by EDTA and HEDTA. I(Cl,swell) blockade by EDTA was pH-dependent. BAPTA blocked I(Cl,swell) also in other cell types. We conclude that Ca(2+) chelating agents block I(Cl,swell) by acting directly on the underlying channel, and that the negative charge of the free chelator form is critical for the blockade.
Lemonnier
L
L
Laboratoire de Physiologie Cellulaire, INSERM EPI 9938, Bât. SN3, USTL, 59655 Villeneuve d'Ascq, France.
Vitko
Y
Y
Shuba
Y M
YM
Vanden Abeele
F
F
Prevarskaya
N
N
Skryma
R
R
D002118:Calcium; D002614:Chelating Agents / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D014407:Tumor Cells, Cultured
D002614:Chelating Agents; D018118:Chloride Channels; D004533:Egtazic Acid; D004492:Edetic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C026060:N-(hydroxyethyl)ethylenediaminetriacetic acid; D002118:Calcium