title: Abnormal tracheal smooth muscle function in the CF mouse.
abstract: Increased airway smooth muscle (ASM) contractility is thought to underlie symptoms of airway hyperresponsiveness (AHR). In the cystic fibrosis (CF) airway, ASM anomalies have been reported, but have not been fully characterized and the underlying mechanisms are largely unknown. We examined ASM in an adult CF mouse tracheal ring preparation, and determined whether changes in contractility were associated with altered ASM morphology. We looked for inherent changes in the cellular pathways involved in contractility, and characterized trachea morphology in the adult trachea and in an embryonic lung culture model during development. Results showed that that there was a reduction in tracheal caliber in CF mice as indicated by a reduction in the number of cartilage rings; proximal cross-sectional areas of cftr (-/-) tracheas and luminal areas were significantly smaller, but there was no difference in the area or distribution of smooth muscle. Morphological differences observed in adult trachea were not evident in the embryonic lung at 11.5 days gestation or after 72 h in culture. Functional data showed a significant reduction in the amplitude and duration of contraction in response to carbachol (CCh) in Ca-free conditions. The reduction in contraction was agonist specific, and occurred throughout the length of the trachea. These data show that there is a loss in the contractile capacity of the CF mouse trachea due to downregulation of the pathway specific to acetylcholine (ACh) activation. This reduction in contraction is not associated with changes in the area or distribution of ASM.
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool Liverpool, U.K.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Wallace
authors.affiliation: Department for Women's and Children's Health, Institute of Translational Medicine, University of Liverpool Liverpool, U.K.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Southern
authors.affiliation: Department for Women's and Children's Health, Institute of Translational Medicine, University of Liverpool Liverpool, U.K.
authors.forename: Marilyn G
authors.initials: MG
authors.lastname: Connell
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool Liverpool, U.K.
authors.forename: Susan
authors.initials: S
authors.lastname: Wray
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool Liverpool, U.K.
authors.forename: Theodor
authors.initials: T
authors.lastname: Burdyga
keywords: Contraction; cystic fibrosis; smooth muscle; trachea