PT  - JOURNAL ARTICLE
AU  - Dortch-Carnes, Juanita
AU  - van Scott, Michael R.
AU  - Fedan, Jeffrey S.
TI  - Changes in Smooth Muscle Tone During Osmotic Challenge in Relation to Epithelial Bioelectric Events in Guinea Pig Isolated Trachea
DP  - 1999 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 911--917
VI  - 289
IP  - 2
4099  - http://jpet.aspetjournals.org/content/289/2/911.short
4100  - http://jpet.aspetjournals.org/content/289/2/911.full
SO  - J Pharmacol Exp Ther1999 May 01; 289
AB  - The relationship between epithelial bioelectric events and epithelium-dependent relaxant and contractile responses of airway smooth muscle in response to hyperosmolar and hypo-osmolar solutions was investigated in guinea pig isolated trachea. Tracheae were perfused with normal or nonisosmotic modified Krebs-Henseleit solution while simultaneously monitoring transepithelial potential difference (VT) and contractile and relaxant responses of the muscle. Baseline VT was −10.1 to −13.3 mV (distal and proximal ends, respectively). Intraluminal amiloride (10−4 M) induced a 3.7-mV depolarization, verifying that the VT was of epithelial origin. Extraluminal methacholine (3 × 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 and prolonged depolarization and epithelium-dependent relaxation. Increasing intraluminal bath osmolarity with sucrose evoked similar responses, except that an immediate, transient hyperpolarization and contraction preceded the depolarization and relaxation. Increasing extraluminal bath osmolarity with 240 mOsM NaCl induced depolarization and a longer lasting epithelium-dependent relaxation, whereas extraluminally added 240 mOsM KCl induced a complex smooth muscle response (i.e., transient relaxation followed by contraction), which was accompanied by prolonged depolarization. Intraluminal hypo-osmolarity produced a transient hyperpolarization followed by depolarization along with contraction of the smooth muscle. Bioelectric responses always preceded smooth muscle responses. These results suggest that bioelectric events in the epithelium triggered by nonisosmotic solutions are associated with epithelium-dependent responses in tracheal smooth muscle. U.S. Government