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Inhibition of volume‐activated chloride currents in endothelial cells by chromones
Author(s) -
Heinke Stephan,
Szücs Géza,
Norris Alan,
Droogmans Guy,
Nilius Bernd
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16629.x
Subject(s) - chemistry , sodium , pipette , patch clamp , nedocromil sodium , tonicity , niflumic acid , biophysics , membrane potential , pharmacology , biochemistry , medicine , receptor , alternative medicine , organic chemistry , pathology , biology , placebo
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 clamp technique. Cl − currents were activated by challenging the cells with a hypotonic extracellular solution of 60% of the normal osmolality. 2 Half maximal activation of the current at +95 mV occurred after exposure of the cells for 148 ± 10 s (n = 6) to hypotonic solution (HTS). At the same membrane potential but in the presence of 100 μ m sodium cromoglycate (disodium‐1, 3‐bis (2′‐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, completely blocked the volume‐activated current in less than 20 s. 4 Sodium cromoglycate, applied at the time when the HTS‐induced current was completely activated, dose‐dependently inhibited this current with a concentration for half maximal inhibition of 310 ±70 μ m . Data for nedocromil sodium were not significantly different from those for sodium cromoglycate. 5 Sodium cromoglycate, loaded into the endothelial cells 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. Intracellulary applied sodium cromoglycate was also more effective and at 50 μ 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‐activated Cl − currents by extracellular sodium cromoglycate may be due to an intracellular action following its permeation across the cell membrane.