Insensitivity of volume-sensitive chloride currents to chromones in human airway epithelial cells.
Chromones (sodium cromoglycate and sodium nedocromil) block cell swelling-activated Cl- channels in NIH-3T3 fibroblasts and endothelial cells. This has led to hypothesize that cell volume regulation might be involved in asthma pathogenesis. Using whole-cell patch-clamp experiments, we studied the effect of chromones on volume-sensitive Cl- currents in transformed human tracheal epithelial cells (9HTEo-) and in primary cultures of human bronchial epithelial cells (BE). Cl- currents activated by hypotonic shock were poorly blocked by extracellular nedocromil or cromoglycate. The block was voltage-dependent since it was observed only at positive membrane potentials. At the concentration of 5 mM, the current inhibition by both chromones at +80 mV was about 40% for 9HTEo- and only 20% for BE. Intracellular application of chromones elicited a voltage-independent inhibition in 9HTEo- cells. Under this condition, volume-sensitive Cl- currents were reduced at all membrane potentials (60 and 45% inhibition by 2 mM nedocromil and cromoglycate respectively). In contrast intracellular chromones were ineffective in BE cells. The relative refractoriness to chromones, in contrast with the high sensitivity shown by other Cl- channels, suggests that the epithelial volume-sensitive Cl- channel is not involved in asthma.
Zegarra-Moran
O
O
Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova, Italy.
Lantero
S
S
Sacco
O
O
Rossi
G A
GA
Galietta
L J
LJ
D016475:3T3 Cells / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D002712:Chlorides / Q000502:physiology*; D004205:Cromolyn Sodium / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D017835:Nedocromil / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D018927:Anti-Asthmatic Agents; D018118:Chloride Channels; D002712:Chlorides; D017835:Nedocromil; D004205:Cromolyn Sodium