title: Sulphonic acid derivatives as probes of pore properties of volume-regulated anion channels in endothelial cells.
abstract: 1. 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). 2. 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. 3. Also suramin and basilen blue induced a voltage dependent current inhibition, reaching a maximum around +40 mV and declining at more positive potentials. 4. The voltage dependence of inhibition was modelled by assuming that these negatively charged molecules bind to a site inside VRAC that senses a fraction delta 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 A2 respectively for the cross-sectional area of the pore.
authors.affiliation: KU Leuven, Laboratorium voor Fysiologie, Campus Gasthuisberg, B-3000 Leuven, Belgium. Guy.Drogmans@MED.KULeuven.ac.be
authors.forename: G
authors.initials: G
authors.lastname: Droogmans
authors.forename: C
authors.initials: C
authors.lastname: Maertens
authors.forename: J
authors.initials: J
authors.lastname: Prenen
authors.forename: B
authors.initials: B
authors.lastname: Nilius
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism*; D047250:Calixarenes; D002417:Cattle; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007536:Isomerism; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011651:Pulmonary Artery; D013451:Sulfonic Acids / Q000737:chemistry* / Q000494:pharmacology*; D013498:Suramin / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014227:Triazines / Q000737:chemistry / Q000378:metabolism
chemical_list: D000838:Anions; D007473:Ion Channels; D046911:Macromolecular Substances; D013451:Sulfonic Acids; D014227:Triazines; D047250:Calixarenes; C012842:Cibacron Blue F 3GA; D013498:Suramin