THEORIES OF THE MECHANISM OF MUSCLE RIGOR 227 



constriction. The dilatation produced by the nitrites is also abolished by 

 iodoacetate but no constriction is seen. These results make it appear that 

 dilatation is an active process requiring energy derived ultimately from 

 glycolysis and oxidations. Although the terminal vasoconstriction may be a 

 form of rigor, there is no evidence on this point. 



THEORIES OF THE MECHANISM OF MUSCLE RIGOR 



The development of rigor following treatment with iodoacetate appears 

 to be a general phenomenon in all types of muscle. Many theories have been 

 suggested but few have survived. On the basis of the evidence presented 

 in the previous sections we can eliminate the following theories from se- 

 rious consideration: (1) that rigor is due to the accumulation of lactate, 



(2) that it is due to either a decrease or increase in the intracellular pH, 



(3) that it is due to the accumulation of methylglyoxal, (4) that it is due 

 to the accumulation of ammonia, (5) that it is brought about by a direct 

 action on the contractile elements, (6) that it is dependent on an increased 

 Ca++ influx, and (7) that it is caused by a depolarization of the muscle 

 membranes. Possibly one or more of these mechanisms contribute in certain 

 instances, but none can explain rigor nor can they be of major importance. 



Until the state of the muscle in rigor is much better known, it will be 

 impossible to formulate mechanisms with any degree of certainty. There is 

 still no general agreement on whether ATP functions in contraction or re- 

 laxation energization, or on whether muscle in rigor cannot relax or is in a 

 state of constant contractile activation, or whether rigor is related or not 

 to normal contraction. Sandow may well be correct in his comparison of 

 rigor and contraction and in his concept that ATP drives the development 

 of rigor, but the evidence is not satisfactory. One problem often overlooked 

 is that total over-all ATP is determined in the muscle, whereas depletion of 

 compartmentalized ATP may be very important. It is true that rigor may 

 begin when the ATP has fallen only 50%, but that ATP measured may be 

 irrelevant to rigor. There is no evidence at all that rigor obtains energy 

 from ATP hydrolysis; ATP decreases before rigor, during rigor, and after 

 rigor, and for causes unassociated with rigor. 



Although admittedly not completely satisfactory, the following mechan- 

 ism is believed to be the most likely from the evidence at hand, and in gen- 

 eral is the one which has been accepted by most workers in the field. The 

 primary action of iodoacetate is on the EM pathway; if an action is exerted 

 on the cycle or oxidations, or if hypoxic conditions exist in the muscle, or 

 if the muscle has a low supply of noncarbohydrate substrate, these will 

 further reduce the energy-supplying reactions. Thus the fundamental effect 

 is an inhibition of ATP generation. Due to the various ATPases and func- 

 tional activity, ATP is slowly or rapidly hydrolyzed; as this occurs, it is 



