204 1. lODOACETATE AND lODOACETAMIDE 



fundamentally on whether the respiration is depressed markedly or not; 

 in the range in which glycolysis is inhibited and respirr.tion is not, the re- 

 covery heat is little changed. Saslow (1936) stated that the recovery heat 

 remains normal as long as the respiration is not reduced to below 50% of 

 normal. Resting heat production is the same in normal and poisoned muscle 

 (Hill and Howarth, 1957). When iodoacetate-treated muscles are stimulat- 

 ed, the heat production rises and remains quite high, even after exhaustion 

 and when the muscle is passing into rigor. If such muscles are placed under 

 anaerobic conditions the heat production falls, but rises again when the 

 muscle is returned to oxygen, indicating the presence of oxidative reactions 

 in the poisoned muscle. "One effect of iodoacetate is to interfere with the 

 mechanism by which the energy released in oxidation can be employed in 

 driving the endothermic reactions necessary for functional recovery" (Cat- 

 tell e« ol, 1931). 



(F) Relation of high-energy phof^phates to rigor. There is a progressive fall 

 in muscle creatine-P and ATP during poisoning with iodoacetate, as initially 

 demonstrated by Lundsgaard (1930 a), and the rate of fall increases with 

 rise in the functional activity of the muscle (Briner et <il., 1959; Carlson 

 and Siger, 1960). The general behavior was previously discussed (page 99) 

 and a summary of results given in Table 1-15, but here we are concerned 

 primarily with the relation to rigor development. Rigor has been most com- 

 monly explained on the basis of depletion of these high-energy substances, 

 but in different ways. The concept that ATP is used for muscle relaxation 

 (Kalckar, 1941) and that ATP is involved in recovery energization, rather 

 than activity energization, can be applied to rigor; the contractile elements 

 cannot relax if there is depletion of ATP. Others believe that ATP is used 

 in the contractile process (including rigor) and that relaxation can be inde- 

 pendent of ATP. Whatever the role of ATP in rigor, it is clear that the 

 kinetics of rigor must be dependent on the relative rates at which ATP is 

 formed and broken down, and thus also on the levels of creatine-P. As far 

 as one can determine, iodoacetate depresses the rate of formation and does 

 not directly affect the rate of utilization, which depends primarily on the 

 state of muscle activity and the various ATPases. 



It is interesting to note that the onset of stiffening in post-mortem rigor 

 appears to be correlated with the disappearance of ATP, and this has been 

 explained in various ways, such as the formation of rather rigid complexes 

 of actomyosin, normally kept apart by ATP. The decrease in the extensi- 

 bility does not begin until the ATP concentration falls to around 2 milli- 

 moles/g, and then proceeds rapidly; the critical level depends on the intra- 

 cellular pH. It has also been suggested that the myofibrillatory ATPase 

 plays no important role in the loss of ATP, either before or during rigor 

 (being well inhibited by the Marsh relaxation factor), and that the sarco- 

 plasmic ATPase perhaps is responsible (Bendall, 1960). 



