Time course of airway mechanics of the (+)insert myosin isoform knockout mouse.
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.
Tuck
Stephanie A
SA
Meakins Christie Laboratories, Department of Medicine, McGill University, 3626 St-Urbain St., Montréal, PQ, H2X 2P2 Canada.
Maghni
Karim
K
Poirier
Annie
A
Babu
Gopal J
GJ
Periasamy
Muthu
M
Bates
Jason H T
JH
Leguillette
Renaud
R
Lauzon
Anne-Marie
AM
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D005260:Female; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000502:physiology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D015656:Respiratory Mechanics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024745:Smooth Muscle Myosins / Q000502:physiology*; D013997:Time Factors
D016085:Bronchoconstrictor Agents; D020033:Protein Isoforms; D012333:RNA, Messenger; D016210:Methacholine Chloride; D024745:Smooth Muscle Myosins; D018995:Myosin Heavy Chains