In striated muscles

Huxley, A.F., Simmons, R. Proposed mechanism of force generation in striated muscle. Nature 233 533-538, 1971. 

G-actin (globular actin) has a molecular weight of about 42 kDa. In higher vertebrates, six isoforms of G-actin, which contain 374/375 residues, are expressed in a cell-specific manner. They are present in striated muscle cells (skeletal and cardiac isoforms), smooth muscle cells (vascular and visceral isoforms) and in non-muscle cells (two isoforms). 

Sarcoplasmic reticulum (SR) is a form of the smoothfaced endoplasmic reticulum (ER) in muscles. It functions as an intracellular Ca2+ store for muscle contraction. Ca2+ is energetically sequestered into the SR by Ca2+-pump/sarcoplasmic endoplasmic reticulum Ca2+-ATPase (SERCA) and released via Ca2+ release channels on stimuli (ryanodine receptor in striated muscles and inositol 1,4,5-trisphosphate receptor in most smooth muscles). Endoplasmic reticulum in non-muscle tissues also functions as an intracellular Ca2+ store. 

In striated muscles, SR is well developed to surround the myofibrils and is divided into two parts, the terminal cisternae (TC) and longitudinal tubules (LT). TC forms triad (skeletal muscle) or dyad (heart) structure with transverse tubules. The ryanodine receptor is located only in the TC, whereas the Ca2+ pump/SERCA is densely packed in both TC and LT. 

Smooth muscles, as the name implies, do not contain sarcomeres. In fact, it was initially difficult to demonstrate the presence of thick filaments in smooth muscle, although their presence is now well-established. On the other hand, it is very difficult to demonstrate thick filaments in highly motile cells, such as macrophages and neutrophils, and this may reflect the necessity to rapidly form and redistribute cytoskeletal elements during migration. Thick filaments in smooth muscles appear to be considerably longer than those in striated muscles. They run diagonally in smooth muscle cells and attach to the membrane at structures known as dense bodies. Thus, there is a cork-screw effect when smooth muscles contract (Warshaw etal., 1987). 

Tropomyosin is thought to lie in the groove formed between the associated actin strands. The sites at which the myosin crossbridges attach are affected by the relationship between tropomyosin and the actin strands. The role of tropomyosin in smooth muscle is completely undefined while in striated muscle it is clearly involved in the activation of contraction. The difference is made clear by the absence from smooth muscle of the protein, troponin, which in striated muscle provides the binding site for the triggering calcium. 

Tropomyosin the Troponin Complex Present in Thin Filaments Perform Key Functions in Striated Muscle... 

In striated muscle, there are two other proteins that are minor in terms of their mass but important in terms of their function. Tropomyosin is a fibrous molecule that consists of two chains, alpha and beta, that attach to F-actin in the groove between its filaments (Figure 49-3). Tropomyosin is present in all muscular and muscle-fike structures. The troponin complex is unique to striated muscle and consists of three polypeptides. Troponin T (TpT) binds to tropomyosin as well as to the other two troponin components. Troponin I (Tpl) inhibits the F-actin-myosin interaction and also binds to the other components of troponin. Troponin C (TpC) is a calcium-binding polypeptide that is structurally and functionally analogous to calmodulin, an important calcium-binding protein widely distributed in nature. Four molecules of calcium ion are bound per molecule of troponin C or calmodulin, and both molecules have a molecular mass of 17 kDa. 

Actin-Based Regulation Occurs in Striated Muscle... 

Smooth muscles have molecular structures similar to those in striated muscle, but the sarcomeres are not aligned so as to generate the striated appearance. Smooth muscles contain a-actinin and tropomyosin molecules, as do skeletal muscles. They do not have the troponin system, and the fight chains of smooth muscle myosin molecules differ from those of striated muscle myosin. Regulation of smooth muscle contraction is myosin-based, unlike striated muscle, which is actin-based. However, like striated muscle, smooth muscle contraction is regulated by Ca. ... 

To what extent does the SR contribute to the rise of [Ca2+]j that activates contraction In other words, what are the relative contributions of the SR and the surface membrane In contrast to the situation in striated muscle where inhibition of SR function abolishes most of contraction, there are several examples in smooth muscle of large amounts of force remaining under these conditions. The SR is an intracellular store of finite capacity. Release of Ca2+ from such a store is well suited to producing transient contractions. However, maintained contraction can be produced by steady state changes in Ca2+ fluxes across the surface membrane. Does the SR make different contributions during different phases of contraction ... 

Somljo It is within the measurement errors. There is a fenestration of the SR sheet, and sticking out come the caveolae. No one has really measured accurately this distance, or the distance between the caveolae and SR on top. The surface coupling space is pretty consistent. With regard to what is different in smooth muscle, if you are talking about the SR at the junction having Ca-ATPase or not, we don t know. What we do know from freeze-fracture studies of striated muscle is that the Ca-ATPase does not seem to be at the SR terminal cisternae. We don t know the answer in smooth muscle, but if there is Ca-ATPase at the junctional surface itself, this is different from what one sees in striated muscle. 

Ca2+] will activate CICR. This represents a substantial departure from coupling processes in striated muscle, as summarized in Fig. 4. 

Wier. Perhaps I can add a few things. The critical point is that the differences will be subtle in time course and difficult to predict on a theoretical basis, without knowing the exact geometrical relationship among the different sources. In striated muscle where we have better information on where sparks might arise, the calculations have shown that it is hard to distinguish a small, in-focus spark, from a large out of focus one. They may have the same amplitude. 

Ryanodine receptors are also localized to both the peripheral and central SR (Fig. 4) in smooth muscle (Lesh et al 1993), and extensive evidence indicates that caffeine releases Ca2+ through ryanodine receptors in smooth muscles, just as in striated muscle (reviewed in lino 2000). Ca2+ influx can also induce Ca2+ release from the SR in smooth muscle (Ganitkevich Isenberg 1995, Kamishima McCarron 1997), suggesting that Ca2+-induced Ca2+ release (CICR) is at least one of the mechanisms, first shown in cardiac muscle (Fabiato 1983), of electromechanical coupling in smooth muscle. 

In smooth muscle, caldesmon plays an analogous role to that of troponin in striated muscle in that it blocks the myosin binding sites. The CaCM complex removes caldesmon from its binding on the thin actin filaments allowing tropomyosin to reposition in the helical grooves of F-actin leading to myosin ATP ase activation. 

When triggering of contraction in striated muscle occurs, the following sequence of processes thus takes place ... 

Smooth muscle differs from skeletal muscle in various ways. Smooth muscles—which are found, for example, in blood vessel walls and in the walls of the intestines—do not contain any muscle fibers. In smooth-muscle cells, which are usually spindle-shaped, the contractile proteins are arranged in a less regular pattern than in striated muscle. Contraction in this type of muscle is usually not stimulated by nerve impulses, but occurs in a largely spontaneous way. Ca (in the form of Ca -calmodulin see p.386) also activates contraction in smooth muscle in this case, however, it does not affect troponin, but activates a protein kinase that phosphorylates the light chains in myosin and thereby increases myosin s ATPase activity. Hormones such as epinephrine and angiotensin II (see p. 330) are able to influence vascular tonicity in this way, for example. 

The possibilities for alternative splicing are enormous. One particularly elaborate example is seen in the gene for tropomyosin in vertebrates. Recall that tropomyosin is a key component of vertebrate striated muscle (see fig. 5.18). The mRNA for tropomyosin found in striated muscle undergoes nine splices in the process of maturation (fig. 31.22). Variants of tropomyosin resulting from alternative splicing are found in other tissues of the same organism. It seems likely... 

Intermediate filament associated proteins (IFAPs) coordinate interactions between intermediate filaments (IFs) and other cytoskeletal elements and organelles, including membrane-associated junctions such as desmosomes and hemidesmosomes in epithelial cells, costameres in striated muscle, and intercalated discs in cardiac muscle. IFAPs thus serve as critical connecting links in the IF scaffolding that organizes the cytoplasm and confers mechanical stability to cells and tissues. However, in recent years it has become apparent that IFAPs are not limited to structural... 

The cortical region of many cells is enriched in actin and associated actin-binding proteins, which function in motility, cell shape maintenance, and membrane protein distribution in polarized cells. In some cases, discrete structures anchor actin to the membrane, as is the case for intercellular adherens junctions and cell-substrate focal contacts. In certain special cell types, the fundamental blueprint for an adherens junction is taken to a new structural level, serving as scaffolding for cell-type specific complexes, such as the dystrophin-associated protein complex (DPC) in striated muscle. Although for years morphological studies have described a close association with IF with the actin-rich cortex, recent advances in methods to study protein-protein interactions have provided new insight into the intimate structural and functional relationship between IFs and these membrane domains. 

---