Increase in passive stiffness at reduced airway smooth muscle length: potential impact on airway responsiveness.
The amplitude of strain in airway smooth muscle (ASM) produced by oscillatory perturbations such as tidal breathing or deep inspiration (DI) influences the force loss in the muscle and is therefore a key determinant of the bronchoprotective and bronchodilatory effects of these breathing maneuvers. The stiffness of unstimulated ASM (passive stiffness) directly influences the amplitude of strain. The nature of the passive stiffness is, however, not clear. In this study, we measured the passive stiffness of ovine ASM at different muscle lengths (relative to in situ length, which was used as a reference length, L(ref)) and states of adaptation to gain insights into the origin of this muscle property. The results showed that the passive stiffness was relatively independent of muscle length, possessing a constant plateau value over a length range from 0.62 to 1.25 L(ref). Following a halving of ASM length, passive stiffness decreased substantially (by 71%) but redeveloped over time ( approximately 30 min) at the shorter length to reach 65% of the stiffness value at L(ref), provided that the muscle was stimulated to contract at least once over a approximately 30-min period. The redevelopment and maintenance of passive stiffness were dependent on the presence of Ca(2+) but unaffected by latrunculin B, an inhibitor of actin filament polymerization. The maintenance of passive stiffness was also not affected by blocking myosin cross-bridge cycling using a myosin light chain kinase inhibitor or by blocking the Rho-Rho kinase (RhoK) pathway using a RhoK inhibitor. Our results suggest that the passive stiffness of ASM is labile and capable of redevelopment following length reduction. Redevelopment and maintenance of passive stiffness following muscle shortening could contribute to airway hyperresponsiveness by attenuating the airway wall strain induced by tidal breathing and DI.
Bossé
Ynuk
Y
James Hogg iCAPTURE Centre/St. Paul's Hospital, 1081 Burrard St., Vancouver, BC, Canada. ybosse@mrl.ubc.ca
Solomon
Dennis
D
Chin
Leslie Y M
LY
Lian
Kevin
K
Paré
Peter D
PD
Seow
Chun Y
CY
D008841:Actin Cytoskeleton / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000033:anatomy & histology*; D015203:Reproducibility of Results; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000033:anatomy & histology* / Q000503:physiopathology*; D012756:Sheep; D054460:rho-Associated Kinases / Q000378:metabolism
D000205:Actomyosin; D054460:rho-Associated Kinases; D002118:Calcium