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

Meakins-Christie Laboratories, Department of Medicine, McGill University, Montréal; Sacre-Cur Hospital, Research Center, Respiratory Division, Université de Montréal, Montréal, Quebec, Canada; Department of Physiology and Cell Biology, Ohio State University, Columbus, Ohio; and Departments of Medicine and Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont

Address correspondence to: Anne-Marie Lauzon, Ph.D., Meakins Christie Laboratories, Department of Medicine, McGill University, 3626 St-Urbain St., Montréal, PQ, H2X 2P2 Canada. 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 (160 µg/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 cm H₂O·s·ml^-1 for KO) nor peak Raw (4.1 ± 0.9 for WT and 4.0 ± 0.5 cm H₂O·s·ml^-1 for KO) differed between groups. However, the time to peak Raw was significantly longer in the KO (17.2 ± 0.6 s) compared with the WT (14.6 ± 0.8 s) mice (P < 0.05). Differentiating Raw with respect to time revealed a greater rate of bronchoconstriction for the WT during the initial 4 s, presumably reflecting the faster shortening velocities under these relatively unloaded conditions. Reverse transcriptase–polymerase chain reaction 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.

Abbreviations: knockout, KO • methacholine, MCh • polymerase chain reaction, PCR • small animal ventilator, SAV • smooth muscle myosin heavy chain, SMMHC • wild-type mice, WT mice

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