Friction in airway smooth muscle: mechanism, latch, and implications in asthma

Fredberg, J. J., K. A. Jones, M. Nathan, S. Raboudi,Y. S. Prakash, S. A. Shore, J. P. Butler, and G. C. Sieck. Friction in airway smooth muscle: mechanism, latch, andimplications in asthma. J. Appl.Physiol. 81(6): 2703-2712, 1996.In muscle,active force and stiffness reflect numbers of actin-myosin interactions and shortening velocity reflects their turnover rates, but the molecular basis of mechanical friction is somewhat less clear. Tobetter characterize molecular mechanisms that govern mechanical friction, we measured the rate of mechanical energy dissipation and therate of actomyosin ATP utilization simultaneously in activated canineairway smooth muscle subjected to small periodic stretches as occur inbreathing. The amplitude of the frictional stress is proportional toE, where E is the tissue stiffness defined by the slope of theresulting force vs. displacement loop and  is the hysteresivitydefined by the fatness of that loop. From contractile stimulus onset,the time course of frictional stress amplitude followed a biphasicpattern that tracked that of the rate of actomyosin ATP consumption.The time course of hysteresivity, however, followed a differentbiphasic pattern that tracked that of shortening velocity. Takentogether with an analysis of mechanical energy storage and dissipationin the cross-bridge cycle, these results indicate, first, that likeshortening velocity and the rate of actomyosin ATP utilization,mechanical friction in airway smooth muscle is also governed by therate of cross-bridge cycling; second, that changes in cycling rateassociated with conversion of rapidly cycling cross bridges to slowlycycling latch bridges can be assessed from changes of hysteresivity ofthe force vs. displacement loop; and third, that steady-state forcemaintenance (latch) is a low-friction contractile state. This lastfinding may account for the unique inability of asthmatic patients to reverse spontaneous airways obstruction with a deep inspiration.