Secondhand smoke inhibits both Cl- and K+ conductances in normal human bronchial epithelial cells.
Secondhand smoke (SHS) exposure is an independent risk factor for asthma, rhinosinusitis, and more severe respiratory tract infections in children and adults. Impaired mucociliary clearance with subsequent mucus retention contributes to the pathophysiology of each of these diseases, suggesting that altered epithelial salt and water transport may play an etiological role. To test the hypothesis that SHS would alter epithelial ion transport, we designed a system for in vitro exposure of mature, well-differentiated human bronchial epithelial cells to SHS. We show that SHS exposure inhibits cAMP-stimulated, bumetanide-sensitive anion secretion by 25 to 40% in a time-dependent fashion in these cells. Increasing the amount of carbon monoxide to 100 ppm from 5 ppm did not increase the amount of inhibition, and filtering SHS reduced inhibition significantly. It was determined that SHS inhibited cAMP-dependent apical membrane chloride conductance by 25% and Ba2+-sensitive basolateral membrane potassium conductance by 50%. These data confirm previous findings that cigarette smoke inhibits chloride secretion in a novel model of smoke exposure designed to mimic SHS exposure. They also extend previous findings to demonstrate an effect on basolateral K+ conductance. Therefore, pharmacological agents that increase either apical membrane chloride conductance or basolateral membrane potassium conductance might be of therapeutic benefit in patients with diseases related to SHS exposure.
Savitski
Amy N
AN
Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. amy.savitski@gmail.com
Mesaros
Clementina
C
Blair
Ian A
IA
Cohen
Noam A
NA
Kreindler
James L
JL
D001980:Bronchi / Q000378:metabolism*; D002478:Cells, Cultured; D002713:Chlorine / Q000378:metabolism*; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D014028:Tobacco Smoke Pollution
D014028:Tobacco Smoke Pollution; D002713:Chlorine; D011188:Potassium