The organization of the thick and thin filaments in muscle cells involves several proteins. Meromyosin and C protein serve as a scaffold for the thick filaments, while nebulin acts as a scaffold for the thin filament. α-actinin anchors the actin filament to the Z line, and tropomodulin regulates the length of the thin filament. These proteins are present in both cardiac and skeletal muscle cells.

Titin, a large elastic protein, tethers the thick filaments to the Z lines. It was initially thought to prevent overstretching of the sarcomere but has also been found to participate in cell signaling. There is evidence suggesting that titin may act as a stretch sensor and modulate protein synthesis in response to stress. Genetic defects in titin can lead to atrophy of both cardiac and skeletal muscle cells, contributing to cardiac dysfunction and skeletal muscle dystrophies (titinopathies). Additionally, titin is believed to contribute to the ability of cardiac muscle to increase force upon stretch.

Connective tissue is more abundant in the heart compared to skeletal muscle. This abundance of connective tissue serves to prevent muscle rupture and overstretching of the heart. Length-tension analysis reveals that cardiac muscle experiences a significant increase in passive tension when stretched beyond its resting length. Skeletal muscle, on the other hand, can tolerate a greater degree of stretch before experiencing a similar increase in passive tension. The reason for this difference is unclear, but it is possible that skeletal muscle stretch is limited by the range of motion of the joint and the surrounding ligaments/connective tissue.

The heart relies on the abundance of connective tissue around cardiac muscle cells to prevent overstretching during periods of increased venous return. During intense exercise, for instance, venous return may increase fivefold. However, the heart can pump this extra volume of blood into the arterial system with only minor changes in ventricular volume. The abundance of connective tissue in the heart limits stretch, and additional regulatory mechanisms assist in pumping the extra blood. If the heart were to be overstretched, the contractile ability of cardiac muscle cells would decrease, leading to insufficient pumping, increased venous pressure, and potentially pulmonary edema.

In cardiac muscle cells, myofibrils are surrounded by the sarcoplasmic reticulum (SR), which is an internal network of membranes. The SR in cardiac muscle is less dense and not as well developed compared to skeletal muscle. The terminal regions of the SR are located near the T tubule or just below the sarcolemma and play a crucial role in the elevation of intracellular calcium concentration during an action potential. However, the mechanism of Ca++ release in the heart differs significantly from skeletal muscle. The heart also contains a high density of mitochondria, occupying up to 30% of its volume. This abundance of mitochondria provides the heart with exceptional oxidative capacity, surpassing that of skeletal muscle.
Several proteins may contribute to the organization of the thick and thin filaments, including meromyosin and C protein (in the center of the sarcomere), which appear to serve as a scaffold for organization of the thick filaments. Similarly, nebulin extends along the length of the actin filament and may serve as a scaffold for the thin filament. The actin filament is anchored to the Z line by α-actinin, whereas the protein tropomodulin resides at the end of the actin filament and regulates the length of the thin filament. These proteins are present in both cardiac and skeletal muscle cells.
The thick filaments are tethered to the Z lines by a large elastic protein called titin. Although titin was postulated to tether myosin to the Z lines and thus prevent overstretching of the sarcomere, there is evidence indicating that titin may participate in cell signaling (perhaps by acting as a stretch sensor and thus modulating protein synthesis in response to stress). Such signaling by titin has been observed in both cardiac and skeletal muscle cells. Moreover, genetic defects in titin result in atrophy of both cardiac and skeletal muscle cells and may contribute to both cardiac dysfunction and skeletal muscle dystrophies (termed titinopathies). Titin is also thought to contribute to the ability of cardiac muscle to increase force upon stretch (discussed in the later section “
Although both cardiac muscle and skeletal muscle contain an abundance of connective tissue, there is more connective tissue in the heart. The abundance of connective tissue in the heart helps prevent muscle rupture (as in skeletal muscle), but it also prevents overstretching of the heart. Length-tension analysis of cardiac muscle, for example, shows a dramatic increase in passive tension as cardiac muscle is stretched beyond its resting length. Skeletal muscle, in contrast, tolerates a much greater degree of stretch before passive tension increases to a comparable level. The reason for this difference between cardiac and skeletal muscle is not known, although one possibility is that stretch of skeletal muscle is typically limited by the range of motion of the joint, which in turn is limited by the ligaments/connective tissue surrounding the joint.
The heart, on the other hand, appears to rely on the abundance of connective tissue around cardiac muscle cells to prevent overstretching during periods of increased venous return. During intense exercise, for example, venous return may increase fivefold. However, the heart is capable of pumping this extra volume of blood into the arterial system with only minor changes in the ventricular volume of the heart (i.e., end-diastolic volume increases less than 20%). Although the abundance of connective tissue in the heart limits stretch of the heart during these periods of increased venous return, additional regulatory mechanisms help the heart pump the extra blood that it receives (as discussed in the section “ ”). Conversely, if the heart were to be overstretched, the contractile ability of cardiac muscle cells would be expected to decrease (because of decreased overlap of the thick and thin filaments), which would result in insufficient pumping, increased venous pressure, and perhaps pulmonary edema.
Within cardiac muscle cells, myofibrils are surrounded by the sarcoplasmic reticulum (SR), an internal network of membranes (see
Fig. 13.1B ). This is similar to the SR in skeletal muscle except that the SR in the heart is less dense and not as well developed. Terminal regions of the SR abut the T tubule or lie just below the sarcolemma (or both) and play a key role in the elevation of intracellular [Ca++] during an action potential. The mechanism by which an action potential initiates release of Ca++ in the heart, however, differs significantly from that in skeletal muscle (as discussed in the section “ ”). The heart contains an abundance of mitochondria; up to 30% of the volume of the heart is occupied by these organelles. The high density of mitochondria provides the heart with great oxidative capacity, more so than is typical in skeletal muscle.