100 



the potential collapsed altogether and contraction ensued. This 

 offers a good opportunity to compare different drugs for their 

 depolarizing action, for the ensuing contraction indicates the in- 

 stant at which the potential was decreased to 55 MV under action 

 of the drug in question, the muscle giving a clear "y^s" or "no" 

 answer. 



If jE* is involved in the energization of the membrane, then 

 drugs which interfere with E* should cause contracture. Hajdu 

 and the author observed that 2,4-dinitrophenol causes contracture 

 in the isolated rat diaphragm muscle. Simultaneously, Barnes and 

 Duff, in England, made the same observation. If this depolarizing 

 action of the 2,4-dinitrophenol was due to its interference with 

 £*, then it could be expected that other related substances which 

 likewise interfere with E* will have the same effect and produce 

 contracture and that their ability to do so will be proportional to 

 their ability to interfere with £*; the latter action can be measured 

 in vitro. 



The results obtained are illustrated by Fig. 25 taken from 

 Hajdu and the author's paper. It shows the kymographic record 

 of a rat diaphragm muscle, excited electrically at two different 

 frequencies. At the arrow, 2,4-dinitro-l-naphthol was added to 

 the saline bathing the muscle. This addition had no immediate 

 effect, but, as the lower curve shows, after a while, the base line 

 started to rise and the muscle went into contracture, the force of 

 which, evenutally, reached twitch tension. These curves give a 

 variety of information. The high tension reached in contracture 

 indicates that there was still plenty of ATP available. As the com- 

 parison of the upper and lower curves shows, the contracture, set- 

 ting in at the same time, was independent of the rate of stimula- 

 tion. The depolarization leading to this contracture was thus inde- 

 pendent of the rapid depolarizations induced by the single electric 

 shocks. Relaxation, i.e., repolarization after these shocks, took 

 place with a normal speed even after the contracture began to set 

 in. The energy transmission involved in the rapid repolarization 



