The Croonian Lecture, 1977 - Stretch activation of muscle: function and mechanism

Abstract

Current theories about the mechanism of muscular contraction suppose that the level of enzymic and contractile activity is controlled by the intracellular concentration of calcium ions, the degree of overlap between the myosin and actin filaments and the rate of relative sliding of the filaments. It is now known that in most or all muscles there is a further direct influence of mechanical conditions, usually called stretch activation; changes of length lead to a delayed change of active tension. The effect is large and functionally significant in insect fibrillar flight muscle and in mammalian heart muscle; it is present, but small, in vertebrate skeletal muscle, which probably accounts for its late discovery. In insect fibrillar flight muscle, the delayed tension is responsible for the rhythmic mechanical activity during flight. In mammalian heart muscle it may play a rôle in Starling’s Law. In insect fibrillar muscle, extension produces a maintained increase in actomyosin ATPase and active tension; in vertebrate skeletal muscle, stretch activation is a transient phenomenon. Mammalian heart muscle shows greater maintenance of stretch activation than skeletal muscle; the duration of higher ATPase activity has not yet been determined. The effective mechanical parameter is not overall strain but is probably the strain on an internal structure related to overall stress. Various lines of evidence point to the myosin filament as the location of the sensor. A considerable degree of molecular synchronization occurs during natural insect flight.

Invertebrate muscles: Thin and thick filament structure; molecular basis of contraction and its regulation, catch and asynchronous muscle

“…These contractions occur because the indirect flight muscles respond to stretch with a brief contraction after the stretch is over (delayed stretch activation). In a complimentary manner, they respond to being shortened with a delayed decrease in force production (Pringle, 1978;Josephson and Ellington, 1997).…”

X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle

“…Lethocerus IFM gives maximal power at normal wing-beat frequencies , but at 20°the stretch activation response is slowed (14,15). We took advantage of the slower kinetics at 20°a nd oscillated the muscles at ∼2 Hz, the frequency at which the work per cycle is maximal (Fig.…”

Myosin light chain-2 mutation affects flight, wing beat frequency, and indirect flight muscle contraction kinetics in Drosophila.

“…In particular, we focused on that part of the active response that corresponds to the phenomenon of stretch induced delayed tension rise, generally referred to as "stretch activation" Stretch activation, common to many types of muscle, is responsible for powering the oscillatory wing movement in insects (Jewell and Ruegg, 1966;Pringle, 1978). This effect can be studied by examining force responses to sinusoidal length perturbations (oscillatory changes in fiber length) applied at different frequencies (Kawai and Brandt, 1980;Thorson and White, 1983).…”

“…The wing beat frequency of Drosophila is determined primarily by the load on the wings and the viscoelastic properties of the cuticle and flight muscle (Pringle, 1978). The wing beat frequency can be lowered by reducing the overall muscle fiber stiffness, which can be accomplished in three fibers (Table HI) and to the unavoidable differences in the compliance of the attachment points for each fiber; most importantly however, fibers from Mlc2 ~3s heterozygotes consistently exhibited a statistically significant reduction (~15 %, Table HI) in bottom frequency as compared to Canton-S and JW60.…”