MEMBRANE CHANGES DURING STLMULAllUN 347 



protoplasmic surface-film, a temporary increase of 

 permeability to water-soluble diffusible substances should 

 be associated with stimulation. The nurnial semi- 

 permeability of the living cell, implying impermeability 

 to water-soluble substances of low molecular wcij^ht 

 (neutral salts, sugars, and amino-acids), depends on 

 the structural continuity of the plasma membrane; and 

 when this continuity is interrupted in any way, the effect 

 is equivalent to a loss of semi-permeability. Such an 

 effect may be temporary and difficult to detect in those 

 cases where the surface-film is rapidly re-formed; but 

 in the more favorable instances we should ex])ect to lind 

 direct evidence of increased permeability during stimula- 

 tion, in addition to the indirect indications afforded by 

 the bioelectric variation and the refractory period. 



According to the present theory, the local electric 

 effects upon which the transmission essential to stimula- 

 tion depends are the result of local alterations of the 

 cell surface, involving increased permeability. Con- 

 versely, therefore, we should expect permeability- 

 increasing agents as a class to cause stimulation of 

 irritable cells. The production of an ''injury-current" 

 by mechanical or other means shows that local interrup- 

 tion in the physical continuity of the cell surface forms 

 a local circuit; and the formation of this circuit may be 

 the means of starting a propagated disturbance or 

 wave of excitation, in the same manner as a local inter- 

 ruption in the surface-film of the passive iron wire starts 

 a wave of activation. It is well known that the ai)plica- 

 tion of a cytolytic, i.e., permeability-increasing, substance 

 to a living tissue produces a local electrical negativity, 

 giving rise to an injury-current, and that this current is 



