EFFECTS ON SKELETAL MUSCLE 209 



merits, but considering the resistance of myosin and actin in vitro and the 

 rather high concentrations used in much of this work, it seems unlikely 

 that there is an important direct action in vivo. 



(J) Is rigor associated with the accumulation of some substance? Rigor from 

 iodoacetate develops faster when the muscle is suspended in a moist chamber 

 instead of being inmiersed in medium, and this has been interpreted to mean 

 that some water-diffusible substance is involved (Lippay and Loning, 1935). 

 The accumulation of methylglyoxal in muscles during iodoacetate poisoning 

 had been shown by Lundsgaard (1930 d) and Barrenscheen et al. (1931), 

 which led Lijtpay and Loning to suspect that this substance might be rig- 

 origenic, but there is no evidence for this and the theory was soon aban- 

 doned. The accumulation of ammonia in muscles in rigor was observed early 

 (Embden and Norpoth, 1931; Norpoth, 1931; Mozolowski et al., 1931), and 

 is now known to result from the sequence of reactions: 



ATP -> ADP -> AMP -> IMP + NH3 



It is simply an expression of the depletion of ATP and is not directly con- 

 cerned with rigor. The most likely explanation for the differences observed 

 in muscles susi^ended in air and in a medium is the accumulation of K+ 

 outside the muscle cells in the former, as Liu et al. (1948) demonstrated 

 (Fig. 1-19). the K' de])olarizing the muscle membranes and facilitating the 

 develoimient of rigor. 



Effects on Neuromuscular Transmission and Acetylcholine Metabolism 



Liasnuieh as the neuromuscular junction or end-plate is a particularly 

 sensitive site for the actions of many substances and since metabolic dis- 

 turbance is known to block junctional transmission before axonal or muscle 

 function is significantly disturbed, what little is known of the effects of 

 iodoacetate will be discussed here so that interpretation of in vivo effects 

 can be put on a broader basis. Hajdu and McDowall (1949) noted that 

 whereas phlorizin blocks the junction selectively, no concentration of iodo- 

 acetate that depresses transmission without poisoning the muscle can be 

 found. Ellis and Beckett (1954) obtained somewhat different results. Iodo- 

 acetate at 0.18 ml/ blocks the response of the diaphragm resulting from 

 phrenic nerve stinnilation before it depresses the muscle directly as long as 

 oxygen is present, and i)yruvate is able to reverse the junctional block. 

 Neuromuscular junction effects could thus be of some significance in the 

 action of iodoacetate in the whole animal. 



It is possible that junctional depression by iodoacetate involves a reduc- 

 tion in the synthesis of acetylcholine. Data on the sensitivity of the choline 

 acetylase system are given in Table 1-34, and it is evident that the final 

 step in the synthesis could well be a site for the action of iodoacetate. In 



