Sulphonic acid derivatives as probes of pore properties of volume‐regulated anion channels in endothelial cells

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Abstract
We have used the whole‐cell patch‐clamp technique to study the effects of 4‐sulphonic‐calixarenes and some other poly‐sulphonic acid agents, such as suramin and basilen blue, on volume‐regulated anion channel (VRAC) currents in cultured endothelial cells (CPAE cells). The 4‐sulphonic‐calixarenes induced a fast inhibition at positive potentials but were ineffective at negative potentials. At small positive potentials, 4‐sulphonic‐calix[4]arene was a more effective inhibitor than 4‐sulphonic‐calix[6]arene and ‐calix[8]arene, which became more effective at more positive potentials. Also suramin and basilen blue induced a voltage dependent current inhibition, reaching a maximum around +40 mV and declining at more positive potentials. The voltage dependence of inhibition was modelled by assuming that these negatively charged molecules bind to a site inside VRAC that senses a fraction δ of the applied electrical field, ranging beween 0.16 to 0.32. 4‐Sulphonic‐calix[4]arene, suramin and basilen blue bind and occlude VRAC at moderate potentials, but permeate the channel at more positive potentials. 4‐Sulphonic‐calix[6]arene and ‐calix[8]arene however do not permeate the channel. From the structural information of the calixarenes, we estimate a lower and upper limit of 11*12 and 17*12 Å2 respectively for the cross‐sectional area of the pore. British Journal of Pharmacology (1999) 128, 35–40; doi:10.1038/sj.bjp.0702770

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