Abstract

Osmotic challenge of airways alters the bioelectric properties of the airway epithelium and induces the release of factors that modulate smooth muscle tone. Recent studies in our laboratory suggested that methacholine-contracted airways relax in response to incremental increases in osmolarity, rather than from cell shrinkage or absolute solute concentration. In the present study, guinea pig tracheae were mounted in Ussing chambers to elucidate the bioelectric effects of challenge of the epithelium with hyperosmolar and isosmolar solutions. Transepithelial short-circuit current (I_sc) across tracheae stimulated with basolateral methacholine was inhibited by apical amiloride, apical 5-nitro-2-(3-phenylpropylamino)benzoic acid, basolateral bumetanide, basolateral ouabain, and Cl^--free solution, but not by basolateral iberiotoxin. Apical hyperosmolar challenge with NaCl variably decreased or increasedI_sc, butl-mannitol (l-M) always inhibitedI_sc; bumetanide attenuated decreases inI_sc. The effects of the transport blockers depended upon whether I_sc was initially decreased or increased. Unique concentration-dependent changes in I_sc and transepithelial resistance (R_t) were observed when ionic (NaCl and KCl), nonionic impermeant (l-M and sucrose), and nonionic permeant (urea) osmolytes were added to the apical and basolateral baths. At concentrations that doubled the osmolarity of the apical bath, l-M, urea, and N-methyl-l-glucamine-gluconate (NMDG-Glu) decreased I_sc. Apical isosmolar NMDG-Glu solution decreased I_sc, and additional NMDG-Glu caused a further decrease in I_sc. Inclusion of one permeant ion, either Na⁺,K⁺, or Cl^-, reversed the response to apical isosmolar and hyperosmolar solutions. Thus, bioelectric responses of the airway epithelium to hyperosmolar solution are induced by incremental increases in osmolarity.