American Journal of Physiology. Cell Physiology vol:275 issue:3 Pt 1 pages:C646-52
We have studied the effects of calixarenes on the volume-regulated anion channel (VRAC) currents in cultured calf pulmonary artery endothelial cells. TS- and TS-TM-calixarenes induced a fast inhibition at positive potentials but were ineffective at negative potentials. Maximal block occurred at potentials between 30 and 50 mV. Lowering extracellular pH enhanced the block and shifted the maximum inhibition to more negative potentials. Current inhibition was also accompanied by an increased current noise. From the analysis of the calixarene-induced noise, we obtained a single-channel conductance of 9.3 +/- 2.1 pS (n = 9) at +30 mV. The voltage- and time-dependent block were described using a model in which calixarenes bind to a site at an electrical distance of 0.25 inside the channel with an affinity of 220 microM at 0 mV. Binding occludes VRAC at moderately positive potentials, but calixarenes permeate the channel at more positive potentials. In conclusion, our data suggest an open-channel block of VRAC by calixarenes that also depends on the protonation of the binding site within the pore.