THE MOLECULAR BASIS OF MUSCLE CONTRACTION 289 



specialized in detail, provide a general mechanistic description of the physi- 

 cal actions of the key molecules which play the vital roles. 



A Theory of Contraction 



One simplified working hypothesis about the physical activity of the con- 

 tractile molecule will now be outlined. It is as though the myosin were a 

 coiled molecule (like other proteins whose structures are known from X-ray 

 diffraction) which, at rest, is held in a stretched condition by virtue of a se- 

 ries of mutually repelling, charged ionic groups along its length, — COOMg + 

 or — NH 3 + , for example. Adsorption of ATP -4 to form the Michaelis- 

 Menten complex, discharges the myosin network, permitting the interatomic 

 restoring forces, which exist because of bent bonds, to relax the molecule to 

 its neutralized (contracted) length. After hydrolysis, ADP" 2 and P" 2 desorb, 

 because they are bound less tightly than ATP -4 and are perhaps aided by 

 other molecular species in the vicinity. After the products have desorbed, 

 the positive charges along the molecule lengthen the coil again, and the 

 molecule is ready to repeat the cycle. 



What is the nature of the trigger which starts ATP -4 adsorbing? The 

 answer is not known, but the hypothesis, based on indirect (but nevertheless 

 substantial) evidence, is that a covering molecule, the "blanket," weakly ad- 

 sorbs on and protects the charged network of the stretched myosin. Its 

 shape is thought to be determined partly by Mg ++ ions, without which the 

 contractile power of myosin ceases. Distortion of the shape of the blanket 

 by the more strongly chelating (complexing) Ca ++ is supposed to bare the 

 myosin to attack by ATP -4 : thus injection of Ca ++ causes contraction. Nerve 

 endings, which run almost to the membranous sheath (sarcolemma) which 

 covers the muscle fibers, are thought by some to be capable of releasing Ca + 

 at the myosin sites via electrochemical stimuli propagated down nerve axons 

 to the nerve ending, and thence down the sheath and in the Z-bands to the 

 myosin sites. 



The connectors between filaments, shown so beautifully in the electron 

 microscope pictures of sliced muscle tissue (Figure 10-13), in this theory take 

 on a very positive character, composition, and role: viz., the ends and par- 

 ticular side groups of stretched myosin molecules, attached at one end to a 

 thin actin filament, but lying within and forming part of an adjacent thick 

 one so that shortening of the myosin molecule itself causes filaments to slide 

 over each other, and the whole tissue to contract. The concept is illustrated 

 in Figure 10-14. Approximate obedience of the whole muscle to Hooke's 

 Law would qualitatively result from behavior on the molecular level. Both 

 the chemistry of the contraction process and the physical sliding of the fibers 

 complement the model. 



