VOL. 4 (1950) MORPHOLOGY IN MUSCLE AND NERVE PHYSIOLOGY 69 



becomes more detailed, eventually leading to the localization of the constituent atoms, 

 the task becomes more that of the crystallographer. The physiologist and biochemist 

 must make use of the information available at the moment in attempting to account 

 for biological phenomena. 



To what extent has structure analj^sis been of assistance in solving major physiolo- 

 gical problems and what is the outlook for further advance in this field? In seeking a 

 perspective regarding such a question a consideration of muscle contraction and nerve 

 conduction may be instructive because of the contrast which these problems present in 

 respect of inherent susceptibility to morphological investigation and to progress already 

 accomplished. The following account is necessarily brief and attempts merely to indicate 



the trend of research in this field. 



* 



MUSCLE CONTRACTION 



Contractility is particularly favourable for morphological study because it involves 

 structural changes at all levels of observation. The voluminous literature of muscle 

 histology, devoted largely to striated muscle, led to few important physiological clues. 

 Perhaps the "reversal of striation"^ on contraction was among the most suggestive. 

 Even observations in polarized light were difficult to interpret. The positive form bire- 

 fringence indicated that the fibrous proteins have widths small with respect to the 

 wavelength of light. The relative isotropy of the / bands was long misinterpreted as 

 indicating disorientation in these regions. Muralt and Edsall's demonstration of the 

 positive birefringence of myosin focused attention on this protein as the contractile 

 substance of muscle. Astbury's identification of myosin as the source of the wide- 

 angle X-ray pattern of muscle, together with his hypothesis of intramolecular folding 

 during contraction, helped to seek in myosin the substratum of contraction^. 



In the short time since electron microscopy has been applied to the problem, im- 

 portant advances have been made. The view that myosin is localized in the A bands, 

 already discredited by quantitative considerations, was disproven by electron micro- 

 scopy, which showed that the protein filaments extend as parallel bundles continuously 

 through both A and / bands*. The relative isotropy of the / bands is therefore not due 

 to disorientation. Recently the view has been taken that the isotropy results from the 

 presence of negatively birefringent substances in the / bands which compensate the 

 positive birefringence of the myosin; this material has been variously reported as 

 nucleotides^' ^, lipids' and phosphoproteins (A'' material)^. 



In contraction the protein filaments remain relatively straight and parallel, indi- 

 cating that the contractile unit is thinner than the filaments (ca 150 A). The distribution 

 of the dense material in the A bands and on the Z membrane changes in agreement with 

 the histological picture of reversal of striation. 



Morphological studies were greatly stimulated by advances in our concepts of 

 mechano-chemical coupling mediated by high-energy phosphate bonds and by the 

 discovery by the Szeged group that myosin is composed of two proteins, a water-soluble 

 myosin and actin, the actomyosin complex being sensitive to the action of adenosine- 

 triphosphate (ATP). The general morphological features of the water-soluble myosin 

 and the globular and fibrous actin were soon demonstrated with the electron microscope®, 

 together with the dissociating effect of ATP on the actomyosin threads^". 



Of great significance in the morphological approach to the contractile mechanism 

 References p. 76lyy. 



