EFFECTS ON SKELETAL MUSCLE 203 



occur if lactate formation is completely inhibited, and Ronzoni and Ehren- 

 fest (1936) found that muscles treated with 0.24 mM iodoacetate maintain 

 reasonably normal respiration for about 100 min, but that an increase is 

 seen when rigor is initiated. This must mean that rigor sets off some process 

 whereby oxidations are accelerated; it is unlikely that the mechanism is 

 ATP depletion, since there is usually a marked fall in ATP before rigor 

 begins (page 204). The excess respiration is not necessary for rigor, inas- 

 much as rigor occurs anaerobically, so that the energy for rigor, if energy 

 is needed, does not arise from these oxidations. There is no evidence that 

 much, if any, ATP is formed by these oxidations, so the electron transport 

 systems may be in an uncoupled state. If 2,4-dinitrophenol is added to 

 iodoacetate-treated muscles, there is marked acceleration of the respiration, 

 but rigor occurs even earlier. 



(D) Potentiation of rigor. It is well known that the effects of iodoacetate 

 on muscle, including the development of rigor, are accelerated and made 

 more severe by anoxia (Ellis and Beckett, 1954) or cyanide (Hsu, 1950), 

 and the obvious explanation is that muscle anaerobically is fully dependent 

 on glycolysis. If rigor is associated with depletion of creatine-P and ATP, 

 as some claim (page 204), 2,4-dinitrophenol should be a particularly effec- 

 tive potentiating agent, and Cori and Cori (1936) have found this to be 

 true. Acetylcholine and K+ produce a rapidly developing rigor* and both 

 accelerate the onset of iodoacetate rigor (von Ledebur, 1932 b; Fleckenstein 

 €t al, 1950). However, this does not indicate direct relationship in the ac- 

 tions of these substances, and the addition of acetylcholine or K+ may 

 merely stimulate the muscle to greater activity, as in a tetanus produced 

 through stimulation of the motor nerve. 



(E) Effect of iodoacetate on heat production in muscle. The initial heat of 

 contraction is not altered by iodoacetate or bromoacetate, but the aerobic 

 or recovery heat may be affected (Fischer, 1931; Cattell et al., 1931). The 

 early discrepant results on this point can probably be explained on the 

 basis of different doses or concentrations used. For example, Fischer (1931), 

 using fairly high concentrations of bromoacetate (1.8-7.2 mM), found that 

 the poisoned muscles exhibit the same heat production aerobically as nor- 

 mal muscles anaerobically, indicating complete depression of aerobic heat 

 production. Cattell et al. (1931), however, found that 0.22 mM iodoacetate 

 does not appreciably alter the heat production, but causes it to occur some- 

 what later after the contraction and to develop more slowly. It depends 



* There may be some doubt if "rigor" is the correct term for this state, inasmuch 

 as it probably differs from post-mortem or iodoacetate rigor, and the term "contrac- 

 ture" may be more appropriate. AcetylchoHne and K+ depolarize the muscle cell 

 membranes and in this respect the contracture may be much more comparable to a 

 normal twitch contraction. 



