Inhibition of volume‐activated chloride currents in endothelial cells by chromones

Stephan Heinke, Géza Szücs, Alan Norris, Guy Droogmans, Bernd Nilius

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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. 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 μm 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). 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. 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 μm. Data for nedocromil sodium were not significantly different from those for sodium cromoglycate. 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 μm caused a decrease in the amplitude of the current to 25 ±6% (n= 10) of the control current. 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. 1995 British Pharmacological Society

Original languageEnglish
Pages (from-to)1393-1398
Number of pages6
JournalBritish journal of pharmacology
Volume115
Issue number8
DOIs
Publication statusPublished - Aug 1995

Keywords

  • Endothelial cells
  • chromones
  • volume‐activated Cl currents

ASJC Scopus subject areas

  • Pharmacology

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