This Article Full Text Full Text (PDF) All Versions of this Article: 2008-0150OCv1 40/1/13    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bossé, Y. Articles by Seow, C. Y. Search for Related Content PubMed PubMed Citation Articles by Bossé, Y. Articles by Seow, C. Y.

Adaptation of Airway Smooth Muscle to Basal Tone

Relevance to Airway Hyperresponsiveness

¹ The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Providence Health Care/St. Paul's Hospital; ² Department of Medicine, Respiratory Division; and ³ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence and requests for reprints should be addressed to Ynuk Bossé, Ph.D., James Hogg iCAPTURE Centre/St. Paul's Hospital, Room 166–1081, Burrard Street, Vancouver, BC, V6Z 1Y6 Canada. E-mail: ybosse{at}mrl.ubc.ca

Lung inflammation and airway hyperresponsiveness (AHR) are hallmarks of asthma, but their interrelationship is unclear. Excessive shortening of airway smooth muscle (ASM) in response to bronchoconstrictors is likely an important determinant of AHR. Hypercontractility of ASM could stem from a change in the intrinsic properties of the muscle, or it could be due to extrinsic factors such as chronic exposure of the muscle to inflammatory mediators in the airways. The latter could be the link between lung inflammation and AHR. The present study was designed to examine the influence of chronic exposure to a contractile agonist on the force-generating capacity of ASM. Force generation in response to electric field stimulation (EFS) was measured in ovine trachealis with or without a basal tone induced by acetylcholine (ACh). While the tone was maintained, the EFS-induced force decreased transiently but increased over time to reach a plateau in approximately 50 minutes. The total force (ACh tone + EFS force) increased monotonically and in proportion to ACh concentration. The results indicate that the muscle adapted to the basal tone and regained its contractile ability in response to a second stimulus (EFS) over time. Analysis suggests that this is due to a cytoskeletal transformation that allows the cytoskeleton to bear force, thus freeing up actomyosin crossbridges to generate more force. Force adaptation in ASM as a consequence of prolonged exposure to the many spasmogens found in asthmatic airways could be a mechanism contributing to AHR seen in asthma.

Key Words: muscle contraction • spasmogen • acetylcholine • muscle tone • asthma

CLINICAL RELEVANCE A basal tone increased the force-generating capacity of airway smooth muscle over time. A tone in asthmatic airways, such as the one induced by inflammatory spasmogens, may foster this force adaptation process and underlie airway hyperresponsiveness.

 

This article has been cited by other articles:

				J. H. T. Bates, S. R. Bullimore, A. Z. Politi, J. Sneyd, R. C. Anafi, and A. -M. Lauzon Transient oscillatory force-length behavior of activated airway smooth muscle Am J Physiol Lung Cell Mol Physiol, August 1, 2009; 297(2): L362 - L372. [Abstract] [Full Text] [PDF]