STIMULATION AND TRANSMISSION 297 



this kind. These are: (i) The bioelectric variations; 

 (2) the presence of a refractory or temporarily inexcitable 

 period immediately following stimulation; and (3) a 

 temporary loss of semi-permeability or increase in the 

 permeability of the cell surface to water-soluble sub- 

 stances. 



We have seen above that the electric current is a 

 universal stimulating agent; and that, conversely, when 

 irritable tissues respond, they give rise to electric currents 

 which traverse the surroundings and may be there 

 detected by appropriate means. Similarly, mechanical or 

 chemical alteration of the cell surface causes excitation 

 and also gives rise to bioelectric currents. Further, during 

 many forms of normal excitation there is direct evidence 

 that the surface layer of protoplasm undergoes a sudden 

 and pronounced change in its properties, one effect of 

 which is to increase the permeability to water-soluble 

 substances; in many cases this change is distinct and 

 easily demonstrated; e.g., the turgor mechanisms of 

 plants, gland cells, and egg cells during activation; in 

 others (nerve, muscle) the indications of changing 

 permeability are indirect. The loss of irritability during 

 the refractory period is also in harmony with the hypoth- 

 esis that the surface layer breaks down or is otherwise 

 altered during stimulation, since semi-permeability, 

 implying electrical polarizability, is apparently essential 

 for stimulation; any temporary loss of semi-permeability 

 must therefore involve loss of irritability. 



The strongest evidence that the surface-change is the 

 essential and primary change in stimulation is the con- 

 stancy with which the foregoing three manifestations of 

 stimulation are associated. Especially significant also 



