New insights into force depression in skeletal muscle

Abstract

SUMMARYForce depression observed following active shortening is not well understood. Previous research suggested that force depression might be associated with a stress-induced inhibition of cross-bridges in the newly formed overlap zone following shortening. Our aim was to investigate this theory in skinned fibres and determine whether there was an inhibition of the attachment of cross-bridges or a decrease in the force produced per cross-bridge. The stress-induced inhibition of cross-bridge theory gives testable predictions, including: (1) skinned fibres should show proportional force and stiffness depression, (2) force after shortening should not be lower than force before shortening, (3) stiffness following shortening should not be lower than stiffness before shortening and (4) force depression should decrease when the stress during shortening is decreased. In agreement with these predictions, force and stiffness depression were approximately proportional, and force depression decreased with decreasing stress during shortening. However, in contrast to the predictions of the stress-induced inhibition of cross-bridge theory, force after shortening from sarcomere lengths of 2.8 and 3.0m to a sarcomere length of 2.4m was smaller than force before shortening, and this was not accompanied by a corresponding decrease in stiffness. We conclude that the stress-induced inhibition of cross-bridge theory, as proposed previously, cannot be the only mechanism for force depression, but that there is an additional, stress-induced inhibition of cross-bridges in the old overlap zone. Furthermore, both mechanisms, inhibition of cross-bridge attachment and reduction of force produced per cross-bridge, contribute to force depression. Inhibition and/or reduction of force depend(s) on the amount of stress imposed on actin during the shortening phase.

Energy cost of isometric force production after active shortening in skinned muscle fibres

“…3) and by others (Joumaa et al, 2012;Lee and Herzog, 2003;Sugi and Tsuchiya, 1988) that force depression after active shortening is correlated with stiffness depression. It is well accepted that stiffness is associated with the number of attached cross-bridges as well as the compliance of actin, myosin and titin (Ford et al, 1981;Goldman and Huxley, 1994;Granzier et al, 2000;Kojima et al, 1994).…”

“…It is well accepted that stiffness is associated with the number of attached cross-bridges as well as the compliance of actin, myosin and titin (Ford et al, 1981;Goldman and Huxley, 1994;Granzier et al, 2000;Kojima et al, 1994). However, it has been assumed that actin, myosin and titin compliance remains constant after active shortening compared with the purely isometric reference contractions; therefore, changes in stiffness are thought to be primarily caused by changes in the number of attached crossbridges (Joumaa et al, 2012;Lee and Herzog, 2003;Sugi and Tsuchiya, 1988). According to the two-state cross-bridge model, this reduction in the number of attached cross-bridges is consistent with our findings that force depression is associated with either a decrease in n while α is maintained or a decrease in α while n is maintained.…”

“…This force depression (FD) has been observed in all muscle preparations, ranging from whole muscles (Abbott and Aubert, 1952;Herzog and Leonard, 1997;Maréchal and Plaghki, 1979;Meijer et al, 1998;Morgan et al, 2000) to human skeletal muscles (De Ruiter et al, 1998;Lee and Herzog, 2003;Power et al, 2014), single fibres (Edman et al, 1993;Granzier and Pollack, 1989;Joumaa et al, 2012;Julian and Morgan, 1979;Minozzo and Rassier, 2013;Sugi and Tsuchiya, 1988) and myofibrils (Joumaa and Herzog, 2010). Force depression increases with increasing shortening magnitudes (Abbott and Aubert, 1952;Herzog and Leonard, 1997;Maréchal and Plaghki, 1979), and decreases with increasing shortening speeds (Abbott and Aubert, 1952;Herzog and Leonard, 1997;Leonard and Herzog, 2005;Maréchal and Plaghki, 1979;Morgan et al, 2000).…”

“…The percentage of stiffness depression was expressed as a function of the stiffness for the purely isometric reference contraction. Fibres that did not show stiffness and force depression were discarded from analysis, as force and stiffness depression was a required outcome for comparison with isometric reference contractions (Joumaa et al, 2012;Lee and Herzog, 2003;Sugi and Tsuchiya, 1988).…”

Effects of series elastic compliance on muscle force summation and the rate of force rise

“…Shortening-induced force depression may arise from a stress-induced inhibition of cross-bridge attachment in newly formed (Maréchal and Plaghki, 1979;Herzog and Leonard, 1997) and old overlap zones (Joumaa et al, 2012). If this mechanism operates when significant internal shortening is permitted under constant-length conditions, it is possible that increasing the effective stiffness of the SEE reduces any inhibition of cross-bridge attachment.…”