Changes in smooth muscle tone during osmotic challenge in relation to epithelial bioelectric events in guinea pig isolated trachea

The relationship between epithelial bioelectric events and epithelium-depen dent relaxant and contractile responses of airway smooth muscle in response to hyperosmolar and hypoosmolar solutions was investigated in guinea pig i solated trachea. Tracheae were perfused with normal or nonisosmotic modifie d Krebs-Henseleit solution while simultaneously monitoring transepithelial potential difference (V-T) and contractile and relaxant responses of the mu scle. Baseline V-T was -10.1 to -13.3 mV (distal and proximal ends, respect ively). Intraluminal amiloride (10(-4) M) induced a 3.7-mV depolarization, verifying that the V-T was of epithelial origin. Extraluminal methacholine (3 x 10(-7) M; EC50) caused hyperpolarization and smooth muscle contraction ; intraluminal methacholine had very little effect. Increasing intraluminal bath osmolarity via addition of 240 mOsM NaCl or KCl caused an immediate a nd prolonged depolarization and epithelium-dependent relaxation. Increasing intraluminal bath osmolarity with sucrose evoked similar responses, except that an immediate, transient hyperpolarization and contraction preceded th e depolarization and relaxation. Increasing extraluminal bath osmolarity wi th 240 mOsM NaCl induced depolarization and a longer lasting epithelium-dep endent relaxation, whereas extraluminally added 240 mOsM KCl induced a comp lex smooth muscle response (i.e., transient relaxation followed by contract ion), which was accompanied by prolonged depolarization. Intraluminal hypo- osmolarity produced a transient hyperpolarization followed by depolarizatio n along with contraction of the smooth muscle. Bioelectric responses always preceded smooth muscle responses. These results suggest that bioelectric e vents in the epithelium triggered by nonisosmotic solutions are associated with epithelium-dependent responses in tracheal smooth muscle.