PHYSIOLOGY OF CARDIAC MUSCLE 



217 



muscle (76). Actin F appears to be a reactant in the 

 contractile process in vivo. 



Actomyosin. As stated above, prolonged saline ex- 

 traction of muscle yields solutions of actomyosin 

 formed by interaction of the two proteins extracted 

 from the myosin rodlets and actin filaments, respec- 

 tively. If solutions of purified F-actin and myosin 

 are mixed at ionic strength greater than 0.3, a sudden 

 rise in viscosity occurs which is reversibly decreased 

 by the addition of ATP. Actin combines nonstoichio- 

 metrically with 3 to 4 parts of myosin by weight to 

 give an actomyosin gel which is insoluble at cellular 

 ionic strength. It appears to be a macromolecule of 

 the order of 20,000,000 in molecular weight. If such 

 a gel is studied in vitro in the presence of low amounts 

 of Mg++ ion, the addition of ATP causes synaeresis 

 and shortening of the gel associated with the splitting 

 of ATP. Both skeletal and cardiac actomyosin behave 

 in this manner. It seems unlikely that such random 

 associations between actin and myosin, as is illus- 

 trated by in vitro gel formation, occur in the intact 

 myofibril in vivo, where these proteins appear to be 

 highly oriented and compartmentalized. 



Tropomyosin. Tropomyosin, the third major myo- 

 fibrillar protein, was isolated by Bailey et al. (9) in 

 1948. Skeletal tropomyosin is a relatively small pro- 

 tein with a molecular weight of 53,000 (240). It is 

 a rigid rod thought by some to be an ideal a-helix 

 with dimensions of 1 2 X 400 A. In pig heart the 

 molecular weight was found to Ije 89,000 (241). 

 Tropomyosin forms dissociable complexes with ribo- 

 nucleic acid to form a nucleotropomyosin. 



Tropomyosin has been found in a wide variety of 

 both striated and smooth muscles in both vertebrate 

 and invertebrate forms. In vertebrate skeletal and 

 smooth muscle it comprises about 10 to 12 per cent 

 of the myofibrillar protein (191) but in cardiac 

 muscle from the pig it amounts to only 4.2 per cent 

 (215). Although tropomyosin undovibtedly has some 

 role in the contractile process its exact function is 

 as yet olxscure. The comparative studies of Sheng c& 

 Tsao (2 1 5) have shown that in general the tropo- 

 myosin content of smooth muscle is higher than that 

 of striated muscle from the same species, and it has 

 been suggested by Bailey (8) that tropomyosin plays 

 a part in the "holding function" of such muscles. 

 In the smooth adductor of the oyster, for example, 

 where tropomyosin comprises about 30 per cent of 

 the total protein, the relaxation phases is very slow- 

 in comparison with the speed of contraction (i). 



Mechanism of contraction. Contraction of a muscle 

 cell is brought about bv a decrease in the length of 



the fibrillar units along the axis of contraction. A 

 theory of contraction will be satisfactory only to the 

 extent that it accounts for all the structural, bio- 

 chemical, and thermodynamic phenomena observable 

 in contracting muscle tis.sue. A striated structure is 

 not essential for contraction, although striated muscle 

 tends to contract with more rapidity and periodicity 

 than smooth muscle. Most of the hypotheses which 

 have been advanced have been designed to account 

 for the molecular events which occur in striated 

 muscle, and are relevant to the events in cardiac 

 muscle. The hypotheses regarding the basic event 

 in the contractile process can be divided into two 

 groups, those that specify "folding"' of one or more 

 of the contractile proteins and those that specify 

 "sliding" of these proteins within the sarcomere to 

 achieve shortening. As further subdivisions, the 

 chemical events in the contractile proteins which are 

 alleged to occur include a) deformation, b) dissocia- 

 tion, and c) phase transition. None of these can, at 

 this time, be said to be generally accepted. The most 

 plausible hypothesis which is currently under con- 

 sideration is one advanced independently by Huxley 

 & Niedergerke (107) and Huxley & Hanson (iii) 

 and elaborated in later papers (106, iio), and this 

 hypothetical mechanism will be presented in detail. 



Electron microscopic studies of the ultrastructure 

 of the mu.scle undergoing passive stretch or contrac- 

 tion down to 60 per cent of resting length reveal little 

 if any change in the length of the A bands. All the 

 change appears to take place in the I bands. At maxi- 

 mum contraction the Z membrane appears to fuse 

 with the edge of the A band and the central H band 

 becomes dense, to give the illusion of a reversal in 

 striation. With maximum shortening (30% of resting 

 length) or in contracture the A band may also shorten 

 appreciably. These changes are shown in figure 17 

 and led to the view that the process of contraction 

 was characterized by the sliding of interdigitating 

 filaments (fig. 18). 



As has been pointed out earlier, two types of fila- 

 ments exist in the myofibril. The thicker ones, 100 A 

 in diameter coincide with the A bands of the sarco- 

 mere and have been shown to consist mainly of myosin 

 (93, 96). The thin filaments appear to originate in 

 the Z membrane and extend toward the center of 

 the sarcomere where they do not, at resting length, 

 meet the opposing thin filaments from the opposite 

 Z membrane. There is some evidence that the thin 

 filaments are connected in the H band by a tenuous 

 S filament. The thin filaments appear to be com- 

 posed mainly of actin (iio, iii). Tropomyosin ap- 



