Filaments muscle physiology

Monomeric G-actin (43 kDa G, globular) makes up 25% of muscle protein by weight. At physiologic ionic strength and in the presence of Mg, G-actin polymerizes noncovalently to form an insoluble double helical filament called F-actin (Figure 49-3). The F-actin fiber is 6-7 nm thick and has a pitch or repeating structure every 35.5 nm. 

In the Z-band, the a-actinin molecules form cross-links between anti-parallel actin filaments. In muscle cross-sections (Fig. 1 IB, C) the square Z-band structure appears in two forms, the basketweave and the small square lattice. These appearances seem to depend on the shape of the cross-links between adjacent anti-parallel actin filaments (called up [U] and down [D] in Figs. 11-14). Some authors believe that the appearance depends on the physiological state of the muscle (e.g., Goldstein et ah, 1988), although this is not certain. A possible mechanism relating the two may be that the small square lattice is simply a basketweave in which the a-actinin cross-links have become bent (Yamaguchi et al., 1985). 

Actin, the major constituent of the thin filaments, exists in two forms. In solutions of low ionic strength it exists as a 42kDa monomer, termed G-actin because of its globular shape. As the ionic strength of the solution rises to that at the physiological level, G-actin polymerizes into a fibrous form, F-actin, that resembles the thin filaments found in muscle. Although actin, like myosin, is an ATPase, the hydrolysis of ATP is not involved in the contraction-relaxation cycle of muscle but rather in the assembly and disassembly of the actin filament. 

The physiology of muscle action and how it is fired are discussed in this book in connection with the mechanism of action of the nervous system (14.4). All that will be said here is that when then above reaction (14.13) run spontaneously in reverse, a supply of energy and protons activates the myofibrils, which are composed of thin filaments made up of the protein actin and thick filaments of the protein myosin. It is the relative movement of these two filaments that is the essence of muscle action. 

To understand the physiological nature of muscle contractions, it is helpful to examine muscles microscopically. Muscle fibers have an outside membrane called the plasmalemma, an interior structure called a sar-colemma, transverse tubules across the fibers, and an inner network of muscle tissue called sarcoplasma. When a nerve impulse reaches the muscle, an action potential is set up and the current quickly travels in both directions from the motor end plate through the entire length of the muscle fiber. The whole inside of the muscle tissue becomes involved as the current spreads and, aided by calcium, the contractile protein called actin causes the muscle component (myosin) to contract. An enzyme, ATP-ase, helps provide the energy needed for the muscular filaments to slide past each other. Relaxation occurs promptly when Ca flows into the muscle tissue and the cycle is completed. The muscle fiber is now ready to be stimulated again by a nerve impulse. 

As the name implies, smooth muscle lacks the highly ordered sarcomere structure of striated muscle, having thick and thin filaments in less orderly arrays with relatively less myosin (one fifth as much) than in striated muscle. Smooth muscle thin filaments have tropomyosin but generally lack troponin. Myosin in smooth muscle is found in monomeric form as well as small thick filaments, and phosphorylation is almost essential for condensation of monomeric myosin into filaments. Thus, the amount of myosin available to cross-bridge with actin may be physiologically adjustable. Like other myosin II types, smooth muscle myosin is a hexamer, and several isoforms of the heavy chains and both light chains are known. The SM-1 isoform (M.W. 204,000) has an unusually long COOH-... 

In vitro, the presence of physiological salt concentrations causes G-actin to polymerize to form the F-actin helix, which in native thin filaments represents the backbone of the filament. Polymerization of G-actin into F-actin can be followed by measuring lightscattering or by viscometry measurements. As in skeletal muscle, polymerization of smooth muscle actin depends on actin concentration, temperature, and ionic conditions (Strzelecka-Golaszewska et al., 1980). For both gizzard and bovine aortic muscle actin, the polymerization rate is optimal at 100 mM KCl and 1 mM MgCl2 (Cavadore et al., 1985). 

The key feature of the TM-dependent inhibition of actin activity by CD is that it takes place at low ratios of CD to actin (see Fig. 6). This high degree of co-operativity is critically dependent on the TM isoform. Smooth muscle TM permits maximal inhibition at a 1 14 ratio, but filaments containing skeletal muscle TM need 1 CD 7 actin for equivalent inhibition (Marston and Redwood, 1993). When CD inhibits actin-TM-activated ATPase at physiological ratios of CD actin, there is no detectable change in the binding of S-1... 

In vitro experimentation has shown that caldesmon is an integral component of smooth muscle thin filaments and plays a central role in their Ca2+-dependent regulation. A mechanism analogous to that of troponin has been proposed this now requires extensive testing. The structure of the regulatory domain of caldesmon is not well defined and we look forward to being able to describe this in three dimensions and in combination with its physiological partners actin, tropomyosin, and calmodulin. 

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