Fig. 6.

Proposed mechanism for the passive force enhancement property of skeletal muscle. In the initial condition, the sarcomere is short and in the passive state (A). If stretched passively from that initial configuration, the sarcomere will become longer and all titin segments are stretched and produce a force in accordance with the titin properties (B). If the sarcomere is activated via calcium but cross-bridge binding to actin is inhibited (for example, by 2,3-butanedione monoxime or by troponin C deletion) and then stretched, calcium will bind to titin (indicated by the brownish color in C) but titin will not bind to actin. Titin is stiffer in this configuration because of the bound calcium. If the sarcomere is stretched while activated and cross-bridge forces are allowed to develop (normal activation and force production, eccentric muscle action), titin will bind calcium and will bind to actin (I propose somewhere in the PEVK region), and will produce more force than in C, because of the titin binding to actin that is made possible by the cross-bridge binding to actin (D). When the actively stretched muscle (in which cross bridges were allowed to bind to actin) is now deactivated, calcium is released from titin and titin will remain bound to actin, thereby producing the passive force enhancement observed in skeletal muscles after stretching of an activated muscle (E). If now, in the deactivated state, the muscle is quickly shortened to its initial length and immediately stretched back to its original length (indicated by double arrow in F), titin is released from actin and the passive force enhancement is immediately abolished, while without this quick shortening-stretch cycle, the passive force enhancement would persist for minutes.