492 PROFESSOR C. R. MARSHALL ON THE 



isotonic solution of di-methyl-di-ethyl-ammonium chloride containing 5 to 10 per 

 cent, alcohol, a strength of alcohol which in itself does not induce contracture, is 

 applied to the muscle, contracture, sometimes marked, is produced. With isotonic 

 solutions of methyl-tri-ethyl-ammonium chloride containing a similar percentage of 

 alcohol, slight contracture results. The addition of the same quantity of alcohol 

 to an isotonic solution of tetra-ethyl-ammonium chloride elicited no contracture of 

 the muscle. 



The previous immersion of the muscle in an isotonic solution of di-methyl-di- 

 ethyl-ammonium chloride, methyl-tri-ethyl-ammonium chloride, or tetra-ethyl- 

 ammonium chloride prevents the contracture ordinarily produced by tetra-methyl- 

 ammonium chloride. The contracture also fails to appear if the muscle be subjected 

 to subminimal concentrations of tetra-methyl-ammonium chloride and the concen- 

 tration be gradually increased, and, as Boehm # showed, if it be previously submitted 

 to a solution of curarin. In my experiments 0"25 per cent, curarin was employed, 

 and the muscle was immersed in it for five minutes. 



In order to determine further the conditions associated with this contracture, a 

 considerable number of experiments were made with the sartorius of the frog. It 

 was found that the best contracture was obtained when the sartorius, after excision, 

 was allowed to remain immersed in 0"6 per cent, sodium chloride in distilled water 

 for fifteen minutes or more, and then submitted to a solution isotonic with it and 

 containing about 0'3 per cent, tetra-methyl-ammonium chloride. Under these 

 conditions the muscle contracts immediately on the addition of the tetra-methyl- 

 ammonium chloride solution and quickly reaches the height obtained with a 

 moderately powerful electrical stimulus (c/. upper tracings of figs. 5 and 6). This 

 extreme contraction may be maintained for ten to twenty seconds, then relaxation, 

 usually rapid at first and often somewhat spasmodic in character, sets in, and the 

 base line is reached within three to four minutes. If the muscle be allowed to 

 remain in the solution no further obvious action occurs, and it is still irritable to 

 moderately powerful electrical stimuli after an immersion of twenty-four hours or 

 more (cf. fig. 8). 



It has already been stated that the smallest concentration of tetra-methyl- 

 ammonium chloride producing contracture was found to be 0*00001 per cent. 

 Greater concentrations than this produce a correspondingly greater amount of 

 contracture, until a concentration of about 0'3 per cent, is reached. Further increase 

 of concentration produces no increased effect, indeed an isotonic solution (l'2 per 

 cent.) usually induces a somewhat smaller effect. 



If the sartorius were not immersed in a saline solution but subjected to the action 

 of a solution of tetra-methyl-ammonium chloride immediately after being arranged 

 in the muscle-chamber, no contracture resulted. This experiment was repeated many 

 times under varying conditions and with different concentrations of tetra-methyl- 



* Arch.f. exp. Path. u. Pharmak., lviii. p. 267 [1908]. 



