EFFECTS ON SKELETAL MUSCLE 195 



1-33. Maynard concluded that iodoacetate markedly increases the uptake 

 of Co^° in most organs and that the effects relate to SH groups in the cell 

 membranes. I would interpret the results quite differently. Since iodoacetate 

 increases the Co^'' in the blood by 57%, it seems likely that an increased 

 organ uptake would result from this. Therefore I calculated the organ/blood 

 ratios and it can be seen that in only two tissues is there an increase, and 

 these increases are small and may not be significant. In two organs — heart 

 and brain — it appears that iodoacetate inhibits the uptake of Co^'' around 

 50%. It may also be mentioned that Maynard found cysteine to decrease 

 the over-all uptake of Co^'^ in all organs, but here the blood level is reduced 

 by over 90%, so that one cannot assume a direct effect on the tissues; it 

 is likely that cysteine reacts with most of the Co^*^ at the site of injection. 

 With respect to iodoacetate, a local inflammatory reaction in the perito- 

 neum may have accounted for the increased absorption of Co^". 



EFFECTS ON SKELETAL MUSCLE 



The earliest investigators of the actions of iodoacetate and related com- 

 pounds emphasized the paralysis and subsequent rigor of voluntary mus- 

 cle; it was soon demonstrated that the action is directly on the muscle. The 

 development of the initial concepts of iodoacetate rigor has been described 

 in the introduction to this chapter. A muscle stimulated to contract in the 

 presence of iodoacetate slowly weakens and loses its excitability, and this 

 is followed by the development of contracture. The initial changes occur 

 sinmltaneously with a depression of glycolysis, which eventually leads to a 

 depletion of the high-energy phosphates in the muscle. The glycolytic de- 

 pression generally has no immediate effect on contractility, and the muscle 

 contracts well as long as it has sufficient ATP. This is reflected in the de- 

 pendence of the rate of onset of rigor on the degree of activity. Thus, a 

 resting muscle may require hours before rigor occurs, whereas with rapid 

 stimulation a few minutes may suffice. The usual course of iodoacetate 

 action may be represented as in Fig. 1-14. The development of contracture 

 is usually irreversible once it has begun, and indeed contracture often occurs 

 even though the iodoacetate is removed from the medium previously, in- 

 dicating that contracture is the end result of a series of changes initially 

 induced by the primary action of iodoacetate. Despite the fact that the 

 earliest interest in iodoacetate centered around the modifications of the 

 state of voluntary muscle, the mechanism by which contracture is produced 

 remains unknown. 



Pattern of a Single Contraction 



Attention has been concentrated mainly on iodoacetate rigor and little 

 studv has been made of the alterations of the normal contraction before 



