Reply from K. A. P. Edman



In a recent Topical Review article experimental evidence was presented elucidating the mechanism underlying the long-lasting enhancement of force that occurs when striated muscle is stretched during tetanic activity (Edman, 2012). In a Letter to the Editor Drs Walter Herzog and Tim Leonard refer to some experimental results, mainly obtained in their own laboratory, that do not support the conclusions reached in the review article. Some of these differences have already been discussed in the above article. I here take up a few points in response to the present comments made by Drs Herzog and Leonard.

One of the key observations detailed in the review article is the finding that a stretch ramp carried out during tetanic stimulation leads to asymmetrical length changes within the two halves of myofibrillar sarcomeres. Such changes occur scattered within the muscle fibre volume resulting in greater filament overlap in one half of the sarcomere than in the opposite sarcomere half. This kind of change, i.e. an increase in myofilament overlap when the muscle is stretched, might appear unrealistic at first glance but is actually a natural consequence of the structural build-up of the sarcomere: a lower resistivity to stretch in one sarcomere half will give an advantage to the opposite half which will get the opportunity to improve its filament overlap, and its force producing capability, during the remainder of the stretch period. Differences in filament overlap between the two halves of individual sarcomeres after active stretch have also recently been reported in isolated myofibrils (Telly et al. 2006; Rassier, 2012; Rassier & Pavlov, 2012).

The asymmetrical changes in filament overlap that arise during active stretch can be expected to be associated with strain of elastic elements to enable segments with reduced filament overlap to match the stronger segments in series. Quick-release measurements performed on intact muscle fibres fully support this view: the strain of damped elastic elements increases in proportion to the residual force enhancement after stretch (see Fig. 3 in Edman, 2012). The origin of the elastic elements involved in this process has not yet been identified but both titin and desmin structures are likely to be involved.

As expressed in the review article, the finding of increased myofilament overlap, in association with strain of passive elastic elements, suggests strongly that that these changes are fundamental in the development of force enhancement after stretch. This, however, does not rule out that active stretch might involve some additional change in the contractile system that affects the mechanical output. Herzog and Leonard point out that their own experimental results indicate that active stretch may slightly enhance the tetanic force (mean increase approximately 4%) above the control value recorded at ‘optimal’ sarcomere length. This is an interesting observation which, however, requires further investigation to be fully understood, as discussed in the review article. According to an earlier study (Edman et al. 1982), based on data from 18 single muscle fibres which were subjected to different stretch amplitudes, no enhancement of force by active stretch could be established within the plateau region of the length–tension relation. A representative recording is illustrated in Fig. 1 of the review article (Edman, 2012).

Regarding the involvement of passive structural elements in force enhancement this has been discussed above and is not elaborated further here. All the evidence suggests that the phenomenon ‘force enhancement after stretch’ is entirely limited to the active period of the muscle fibre. It is induced by an active stretch ramp and it disappears completely after the fibre is given time to relax fully. Thus with the moderate stretch amplitudes generally used in these experiments there is no remaining effect on the resting tension.

The phenomenon ‘residual force enhancement after stretch’ is based on studies of intact muscle preparations, mainly intact single muscle fibres, and it is unclear whether this phenomenon is fully reproducible on isolated myofibrils. The latter preparations are lacking the tissue components that keep the myofibrils in register in the muscle fibre, components that are likely to be involved in the contractile response to active stretch. To this may be added the observation that the isolated myofibril lacks the stability and repeatability when activated that characterizes the single fibre preparation, as pointed out in the review article.