Nature of Chemical Stimulation. 171 



stances that influence colloidal aggregation-state; such substances 

 ought, as a class, to show evident relations to stimulation. Again, 

 substances with a specific action on lipoids should also show such 

 relations. These two classes of substances, electrolytes and lipoid- 

 solvents, do in fact show peculiar relations to the stimulation-proc- 

 ess; their solutions affect the irritable tissue in two distinct ways; 

 either (1) they stimulate, or (2) without stimulating directly they 

 facilitate or hinder stimulation by other means — in other words, 

 they sensitize or desensitize the tissue. This means, in terms of the 

 present hypothesis, that such substances either (1) produce rapid 

 increase in the permeability of the plasma-membrance, or (2) alter 

 the readiness with which this change is produced by other means 

 increasing on the one hand (sensitization), or decreasing on the 

 other (desensitization), the liability to such sudden increase of 

 permeability. 



In normal or electrical stimulation the increase of permeability 

 is completely and readily reversible, the tissue returning immedi- 

 ately to the resting state on cessation of the stimulus. In contrast 

 to such a condition, many forms of chemical stimulation are found 

 to be imperfectly reversible or, in some cases, completely irrever- 

 sible. A distinction must, therefore, be made between reversible 

 and irreversible chemical stimulation. This distinction is illus- 

 trated, in the case of frog's skeletal muscle, by the following classi- 

 fication: 



f Stimulation by isotonic solutions of neutral sodium salts, and 

 -j by various other solutions of neutral salts of alkali metals 

 (. (solutions producing spontaneous twitching), 

 f 1. Stimulation by solutions of salts of heavy metals, strong acid 



or alkali, ammonia, etc. 

 ! 2. Stimulation by concentrated solutions of lipoid-solvents 

 1 (as chloroform). 



I 3. Stimulation by hemolytics (as saponin), or similarly acting 

 (. substances (including certain bacterial toxins, as tetanolysin). 



In the solutions of Class A, the muscle typically exhibits 

 rhythmical and often energetic twitching, i. e., alternation of con- 

 traction and relaxation, and in some cases increase of tone; on 

 return to Ringer's solution, relaxation follows promptly; the nor- 

 mal properties of the tissue remain essentially unaltered. In the 

 solutions of Class B, the contraction is typically slow and steady 

 without twitching, and the contracted state, once attained, persists 



Reversible 



A. chemical 

 stimulation. 



Irreversible 



B. chemical 

 stimulation. 



