INHIBITION OF VOLUME-ACTIVATED CHLORIDE CURRENTS IN ENDOTHELIAL-CELLSBY CHROMONES

1 We have studied the effects of the reported chloride channel blocker , sodium cromoglycate, on volume-activated Cl- currents in endothelial cells from bovine pulmonary artery by means of the whole-cell patch c lamp technique. Cl- currents were activated by challenging the cells w ith a hypotonic extracellular solution of 60% of the normal osmolarity . 2 Half maximal activation of the current at + 95 mV occurred after e xposure of the cells for 148 +/- 10 s (n = 6) to hypotonic solution (H TS). At the same membrane potential but in the presence of 100 mu M so dium cromoglycate (disodium-1,3-bis -carboxylate-chromone-5'-yloxy)-2- hydroxy-propane) activation was delayed (253 +/- 25 s, n = 6) and the maximal current amplitude was reduced to 63 +/- 7% of the control (n = 13). 3 In comparison, an equimolar concentration of NPPB (5-nitro-2(3 -phenyl) propylamino-benzoic acid), another Cl- channel blocker, compl etely blocked the volume-activated current in less than 20 s. 4 Sodium cromoglycate, applied at the time when the HTS-induced current was co mpletely activated, dose-dependently inhibited this current with a con centration for half maximal inhibition of 310 +/- 70 mu M. Data for ne docromil sodium were not significantly different from those for sodium cromoglycate. 5 Sodium cromoglycate, loaded into the endothelial cell s via the patch pipette in ruptured patches, resulted in a decline of the HTS activated current with a time course that was compatible with diffusion of the compound from the pipette into the cell. Intracellula ry applied sodium cromoglycate was also more effective and at 50 mu M caused a decrease in the amplitude of the current to 25 +/- 6% (n = 10 ) of the control current. 6 It is concluded that blockade of volume-ac tivated Cl- currents by extracellular sodium cromoglycate may be due t o an intracellular action following its permeation across the cell mem brane.