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

Stephanie A. Tuck, Karim Maghni, Annie Poirier, Gopal J. Babu, Muthu Periasamy, Jason H.T. Bates, Renaud Leguillette, Anne Marie Lauzon

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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 H 2O·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.

Original languageEnglish (US)
Pages (from-to)326-332
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume30
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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