Time course of airway mechanics of the (+)insert myosin isoform knockout mouse

Am J Respir Cell Mol Biol. 2004 Mar;30(3):326-32. doi: 10.1165/rcmb.2003-0254OC. Epub 2003 Sep 4.


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 microg/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(2)O.s.ml(-1) for KO) nor peak Raw (4.1 +/- 0.9 for WT and 4.0 +/- 0.5 cm H(2)O.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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bronchoconstriction / drug effects
  • Bronchoconstriction / physiology*
  • Bronchoconstrictor Agents / administration & dosage
  • Female
  • Male
  • Methacholine Chloride / administration & dosage
  • Mice
  • Mice, Knockout
  • Muscle, Smooth / physiology
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / physiology*
  • Protein Isoforms / physiology
  • RNA, Messenger / metabolism
  • Respiratory Mechanics / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smooth Muscle Myosins / physiology*
  • Time Factors


  • Bronchoconstrictor Agents
  • Protein Isoforms
  • RNA, Messenger
  • Methacholine Chloride
  • Smooth Muscle Myosins
  • Myosin Heavy Chains