Novobiocin forms cation-permeable ion channels in rat fetal distal lung epithelium.
The antibiotic novobiocin has been previously reported to increase Na+ transport in frog skin, presumably by attenuation of Na+ self-inhibition of Na+ channels. To determine whether novobiocin had similar effects and utilized a similar mechanism in mammalian Na(+)-transporting tissues, we studied its effect on ion transport by primary cultures of fetal distal lung epithelium (FDLE) cultured from 20-day gestationally aged rats (term = 22 days). Novobiocin (10 mM) increased short-circuit current and markedly decreased the resistance in FDLE monolayers mounted in Ussing chambers. Fura-2 single-cell studies showed that novobiocin increased intracellular Ca2+ concentration and that this resulted from extracellular sources. Nystatin-perforated patch-clamp techniques demonstrated that novobiocin increased nonrectifying cation whole cell currents without inducing detectable anion currents. Novobiocin created nonrectifying monovalent cation-selective channels in lipid bilayers. These studies demonstrated that novobiocin affects the bioelectric properties of Na+ transporting lung epithelium and that this likely occurs by the formation of ion-permeant channels in their lipid membranes.
O'Brodovich
H
H
Division of Respiratory Research, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Wang
X
X
Li
C
C
Rafii
B
B
Correa
J
J
Bear
C
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000493:pharmacokinetics*; D004594:Electrophysiology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D005333:Fetus / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D009675:Novobiocin / Q000494:pharmacology*; D010539:Permeability; D051381:Rats
D002412:Cations; D007473:Ion Channels; D008051:Lipid Bilayers; D009675:Novobiocin; D002118:Calcium