Troponin C has four binding sites for Ca++. Two of these sites have a high affinity for Ca++, while also binding Mg++ at rest. These sites are involved in controlling and enhancing the interaction between the troponin I and troponin T subunits. The other two binding sites have a lower affinity for Ca++ and bind Ca++ as its concentration increases after release from the SR. The increase in tension in contractile force occurs in a sigmoidal manner as intracellular [Ca++] rises above 0.1 µM, with half-maximal force occurring at less than 1 µM Ca++. The mechanism by which Ca++ promotes this increase in tension is as follows: Ca++ released from the SR binds to troponin C. Once bound with Ca++, troponin C facilitates the binding of myosin to the actin filaments. The binding of myosin to actin filaments appears to cause a further shift in tropomyosin. Although a given tropomyosin molecule extends over seven actin molecules, it is hypothesized that the strong binding of myosin to actin results in movement of an adjacent tropomyosin molecule, perhaps exposing myosin binding sites on as many as 14 actin molecules. This ability of one tropomyosin molecule to influence the movement of another may be a consequence of the close proximity of adjacent tropomyosin molecules. Once myosin and actin are bound, ATP-dependent conformational changes in the myosin molecule result in movement of the actin filaments toward the center of the sarcomere, shortening its length and contracting the muscle fiber. The mechanism by which myosin produces force and shortens the sarcomere involves four steps collectively termed the cross-bridge cycle. In the resting state, myosin is thought to have partially hydrolyzed ATP. When Ca++ is released from the terminal cisternae of the SR, it binds to troponin C, promoting movement of tropomyosin on the actin filament to expose myosin-binding sites on actin. This allows the "energized" myosin to bind to actin and initiate the cross-bridge cycle.
Fig. 12.12 ”). Troponin C has four Ca++ binding sites. Two contractile force (i.e., tension) increases in a sigmoidal of these sites have high affinity for Ca++ but also bind manner as intracellular [Ca++] is elevated above 0.1 µM, Mg++ at rest. These sites seem to be involved in control-with half-maximal force occurring at less than 1 µM Ca++ . ling and enhancing the interaction between the troponin The mechanism by which Ca++ promotes this increase in I and troponin T subunits. The other two binding sites tension is as follows: Ca++ released from the SR binds to have lower affinity and bind Ca++ as its concentration rises troponin C. Once bound with Ca++ , troponin C facilitates after release from the SR. Binding of myosin to the actin • Fig. 12.11. Identification of three endogenous micropeptides that inhibit sarcoplasmic endoplasmic reticulum Ca++-ATPase (SERCA; A), and their predicted organization in the SR membrane (B). MLN, myoregulin; PLN, phospholamban; SCL, sarcolamban; SLN, sarcolipin. (Modified from Anderson DM, et al. A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell. 2015;160:595-606.) 0 0.01 0.1 1 10 100 • Fig. 12.12. The contractile force of skeletal muscle increases in a Ca++-dependent manner as a result of binding of Ca++ to troponin C and the subsequent movement of tropomyosin away from myosin binding sites on the underlying actin molecules. See text for details. (Redrawn from Hartshorne DJ. In Lapedes DN. ed. Yearbook of Science and Technology. New York: McGraw-Hill; 1976.) filaments appears to cause a further shift in tropomyosin. Although a given tropomyosin molecule extends over seven actin molecules, it is hypothesized that the strong binding of myosin to actin results in movement of an adjacent tropomyosin molecule, perhaps exposing myosin binding sites on as many as 14 actin molecules. This ability of one tropomyosin molecule to influence the movement  of another may be a consequence of the close proximity of adjacent tropomyosin molecules.
Cross-Bridge Cycling: Sarcomere Shortening
Once myosin and actin are bound, ATP-dependent conformational changes in the myosin molecule result in movement of the actin filaments toward the center of the sarcomere. Such movement shortens the length of the sarcomere and thereby contracts the muscle fiber. The mechanism by which myosin produces force and shortens the sarcomere is thought to involve four basic steps that are collectively termed the cross-bridge cycle (labeled a to d in
Fig. 12.13 ). In the resting state, myosin is thought to have partially hydrolyzed ATP (state a). When Ca++ is released from the terminal cisternae of the SR, it binds to troponin C, which in turn promotes movement of tropomyosin on the actin filament in such a way that myosin-binding sites on actin are exposed. This then allows the “energized”