Direct modulation of volume-regulated anion channels by Ca(2+) chelating agents.

Abstract

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.

• Authors: L Lemonnier, Y Vitko, Y M Shuba, F Vanden Abeele, N Prevarskaya, R Skryma
• Journal: FEBS letters (FEBS Lett) Vol. 521 Issue 1-3 Pg. 152-6 (Jun 19 2002) ISSN: 0014-5793 [Print] England
• PMID: 12067708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chelating Agents
• Chloride Channels
• Egtazic Acid
• Edetic Acid
• 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
• N-(hydroxyethyl)ethylenediaminetriacetic acid
• Calcium

Topics

• Calcium
• Chelating Agents (pharmacology)
• Chloride Channels (antagonists & inhibitors, physiology)
• Edetic Acid (analogs & derivatives, pharmacology)
• Egtazic Acid (analogs & derivatives, pharmacology)
• Humans
• Hydrogen-Ion Concentration
• Tumor Cells, Cultured