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Published ahead of print on September 4, 2003, doi:10.1165/rcmb.2003-0254OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 3, March 2004, 326-332

A more recent version of this article appeared on March 1, 2004
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Submitted on July 7, 2003
Revised on September 2, 2003

Time Course of Airway Mechanics of the (+)InsertMyosin Isoform Knockout Mouse

Stephanie A Tuck1, Karim Maghni2, Annie Poirier2, Gopal J Babu3, Muthu Periasamy3, Jason H Bates4, Renaud Leguillette1, and Anne-Marie Lauzon1*

1 Department of Medicine, Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada, 2 Sacre-Coeur Hospital, Universite de Montreal, Montreal, Quebec, Canada, 3 Department of Physiology and Cell Biology, Ohio State University, Columbus, Ohio, USA, 4 Departments of Medicine and Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA

* To whom correspondence should be addressed. E-mail: anne-marie.lauzon{at}mcgill.ca.

Two smooth muscle myosin heavy chain isoforms that differ by the presence ((+)insert or the absence ((-)insert) of a 7 amino acid insert in the motor domain have a 2-fold difference in their in vitro actin filament velocity. We hypothesized that a preferential expression of the fast (+)insert isoform in airway smooth muscle would increase the rate of bronchoconstriction. To verify our hypothesis we measured the time course of bronchoconstriction following a bolus injection of methacholine (160µg/kg) in (+)insert isoform knockout (KO) and corresponding wild-type (WT) mice. Neither baseline airway resistance (Raw) (0.424±0.04 for WT and 0.374±0.01 cmH2O s ml-1 for KO) nor peak Raw (4.1±0.9 for WT and 4.0±0.5cmH2O s ml-1 for KO) differed between groups. However, the time to peak Raw was significantly longer in the KO (17.2±0.6s) compared to the WT (14.6±0.8s) mice (p<0.05). Differentiating Raw with respect to time revealed a greater rate of bronchoconstriction for the WT during the initial 4s, presumably reflecting the faster shortening velocities under these relatively unloaded conditions. RT-PCR analysis revealed that the (+)insert myosin isoform mRNA content in the WT airways was 47.8±5.6%. We conclude that the presence of the (+)insert myosin isoform in the airways increases the rate of bronchoconstriction.




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