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

S. Heinke, G. Szücs, A. Norris, G. Droogmans, B. Nilius

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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 osmolarity. 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 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). 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 μM. 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 μM 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.

Original languageEnglish
Pages (from-to)1393-1398
Number of pages6
JournalBritish Journal of Pharmacology
Volume115
Issue number8
Publication statusPublished - 1995

Fingerprint

Chromones
Cromolyn Sodium
Chlorides
Hypotonic Solutions
Endothelial Cells
Nedocromil
Propane
Chloride Channels
Benzoic Acid
Patch-Clamp Techniques
Membrane Potentials
Osmolar Concentration
Pulmonary Artery
Cell Membrane

Keywords

  • Chromones
  • Endothelial cells
  • Volume-activated Cl currents

ASJC Scopus subject areas

  • Pharmacology

Cite this

Inhibition of volume-activated chloride currents in endothelial cells by chromones. / Heinke, S.; Szücs, G.; Norris, A.; Droogmans, G.; Nilius, B.

In: British Journal of Pharmacology, Vol. 115, No. 8, 1995, p. 1393-1398.

Research output: Contribution to journalArticle

Heinke, S, Szücs, G, Norris, A, Droogmans, G & Nilius, B 1995, 'Inhibition of volume-activated chloride currents in endothelial cells by chromones', British Journal of Pharmacology, vol. 115, no. 8, pp. 1393-1398.
Heinke, S. ; Szücs, G. ; Norris, A. ; Droogmans, G. ; Nilius, B. / Inhibition of volume-activated chloride currents in endothelial cells by chromones. In: British Journal of Pharmacology. 1995 ; Vol. 115, No. 8. pp. 1393-1398.
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N2 - 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 osmolarity. 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 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). 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 μM. 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 μM 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.

AB - 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 osmolarity. 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 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). 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 μM. 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 μM 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.

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