Opposing pairs of an even longer template protein, called titin, position the thick filaments midway between the Z discs. Titin acts as a molecular spring, with a long series of immunoglobulin-like domains that can unfold one by one as stress is applied to the protein. A springlike unfolding and refolding of these domains keeps the thick filaments poised in the middle of the sarcomere and allows the muscle fiber to recover after being overstretched. In C. elegans, whose sarcomeres are longer than those in vertebrates, titin is longer as well, suggesting that it serves also as a molecular ruler, determining in this case the overall length of each sarcomere.
The force-generating molecular interaction between myosin thick filaments and actin thin filaments takes place only when a signal passes to the skeletal muscle from the nerve that stimulates it. Immediately upon arrival of the signal, the muscle cell needs to be able to contract very rapidly, with all the sarcomeres shortening simultaneously. Two major features of the muscle cell make extremely rapid contraction possible. First, as previously discussed, the individual myosin motor heads in each thick filament spend only a small fraction of the ATP cycle time bound to the filament and actively generating force, so many myosin heads can act in rapid succession on the same thin filament without interfering with one another. Second, a specialized membrane system relays the incoming signal rapidly throughout the entire cell. The signal from the nerve triggers an action potential in the muscle cell plasma membrane (discussed in Chapter 11), and this electrical excitation spreads swiftly into a series of membranous folds—the transverse tubules, or T tubules—that extend inward from the plasma membrane around each myofibril. The signal is then relayed across a small gap to the sarcoplasmic reticulum, an adjacent weblike sheath of modified endoplasmic reticulum that surrounds each myofibril like a net stocking (Figure 16–35A and B).
When the incoming action potential activates a Ca2+ channel in the T-tubule membrane, Ca2+ influx triggers the opening of Ca2+-release channels in the sarcoplasmic reticulum (Figure 16–35C). Ca2+ flooding into the cytosol then initiates the contraction of each myofibril. Because the signal from the muscle cell plasma membrane is passed within milliseconds (via the T tubules and sarcoplasmic reticulum) to every sarcomere in the cell, all of the myofibrils in the cell contract at once. The increase in Ca2+ concentration is transient because the Ca2+ is rapidly pumped back into the sarcoplasmic reticulum by an abundant, ATP-dependent Ca2+-pump (also called a Ca2+-ATPase) in its membrane (see Figure 11–13). Typically, the cytoplasmic Ca2+ concentration is restored to resting levels within 30 msec, allowing the myofibrils to relax. Thus, muscle contraction depends on two processes that consume enormous amounts of ATP: filament sliding, driven by the ATPase of the myosin motor domain, and Ca2+ pumping, driven by the Ca2+pump.
Figure 16–34 Organization of accessory proteins in a sarcomere. Each giant titin molecule extends from the Z disc to the  M line—a distance of over 1 μm. Part of each titin molecule is closely associated with a myosin thick filament (which switches polarity at the M line); the rest of the titin molecule is elastic and changes length as the sarcomere contracts and relaxes. Each nebulin molecule is exactly the length of a thin filament. The actin filaments are also coated with tropomyosin and troponin (not shown; see Figure 16–36) and are capped at both ends. Tropomodulin caps the minus end of the actin filaments, and CapZ anchors the plus end at the Z disc, which also contains α-actinin (not shown).