AJP - Cell Physiology, Vol 264, Issue 6 C1532-C1537, Copyright © 1993 by American Physiological Society
Novobiocin forms cation-permeable ion channels in rat fetal distal lung epithelium
H. O'Brodovich, X. Wang, C. Li, B. Rafii, J. Correa and C. Bear
Division of Respiratory Research, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
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.
