Submucosal tissues modulate the bioelectric properties of airway epithelium

Exposure of isolated canine tracheal epithelium to acetylcholine (Ach) increased transepithelial conductance (GT) and short-circuit current (ISC). Qualitatively different responses were obtained when the epithelium was studied as a part of an intact posterior tracheal membrane that contained smooth muscle. Ach decreased GT, did not affect ISC, and induced a 2-fold increase in measured tension. In these tissues, baseline GT was enhanced compared with that of isolated epithelium. Indomethacin inhibited the Ach-induced responses of isolated epithelium but did not alter the responses of intact airway tissue. The epithelial origin of these electrophysiologic responses was confirmed in experiments that showed that denudation of intact tracheal tissue greatly increased base-line GT, eliminated ISC, abolished the electrophysiologic response to Ach, and enhanced Ach-induced smooth muscle constriction. The qualitatively different responses to Ach of intact tracheal membrane and epithelium alone suggest that the behavior of airway epithelia in the whole animal may be significantly different from that observed in conventional in vitro studies of isolated epithelia.