Friction in airway smooth muscle: mechanism, latch, and implications in asthma.
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. To better characterize molecular mechanisms that govern mechanical friction, we measured the rate of mechanical energy dissipation and the rate of actomyosin ATP utilization simultaneously in activated canine airway smooth muscle subjected to small periodic stretches as occur in breathing. The amplitude of the frictional stress is proportional to eta E, where E is the tissue stiffness defined by the slope of the resulting force vs. displacement loop and eta is the hysteresivity defined by the fatness of that loop. From contractile stimulus onset, the time course of frictional stress amplitude followed a biphasic pattern that tracked that of the rate of actomyosin ATP consumption. The time course of hysteresivity, however, followed a different biphasic pattern that tracked that of shortening velocity. Taken together with an analysis of mechanical energy storage and dissipation in the cross-bridge cycle, these results indicate, first, that like shortening velocity and the rate of actomyosin ATP utilization, mechanical friction in airway smooth muscle is also governed by the rate of cross-bridge cycling; second, that changes in cycling rate associated with conversion of rapidly cycling cross bridges to slowly cycling latch bridges can be assessed from changes of hysteresivity of the force vs. displacement loop; and third, that steady-state force maintenance (latch) is a low-friction contractile state. This last finding may account for the unique inability of asthmatic patients to reverse spontaneous airways obstruction with a deep inspiration.
Fredberg
J J
JJ
Department of Environmental Health, Harvard School of Public Health, Boston, Massachsetts 02115, USA. jfredber@hsph.harvard.edu
Jones
K A
KA
Nathan
M
M
Raboudi
S
S
Prakash
Y S
YS
Shore
S A
SA
Butler
J P
JP
Sieck
G C
GC
D000403:Airway Resistance / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D004285:Dogs; D017276:Friction; D009130:Muscle, Smooth / Q000502:physiology*; D014132:Trachea / Q000502:physiology*