STIMULATION OF LIVING ORGANISMS 587 



rapid loss of a yellow coloring matter from certain cells forming part of 

 the body. Apparently any change of condition, chemical or other, that 

 increases the permeability of these cells sufficiently to cause a rapid loss 

 of pigment causes also strong stimulation of the irritable elements. It 

 is possible to prevent the stimulating effect of the salt solution by 

 anesthetics or by certain other salts, e. g., calcium or magnesium chlo- 

 ride; and at the same time the change in the pigment-containing cells 

 is also prevented. Eapid increase of permeability and strong stimulation 

 thus show a definite parallelism. Other widespread phenomena, such as 

 the refractory or inexcitable period shown by all irritable tissues immedi- 

 ately after stimulation, point in the same direction. There is indeed an 

 unusually broad basis of biological fact for the inference that in irritable 

 tissues the plasma membranes undergo a sudden and well-marked in- 

 crease of permeability during stimulation — i. e., lose their semipermea- 

 bility for a brief time, the exact duration of which varies characteristic- 

 ally for different tissues. 



Stimulation appears always to be accompanied by a change in the 

 electrical properties of the irritable elements ; and there is every indica- 

 tion that the characteristic negative variation or action current is an 

 expression or consequence of the above change in the membranes. As 

 already pointed out, any semipermeable partition or membrane separa- 

 ting two electrolyte solutions becomes the seat of an electrical polariza- 

 tion, whose degree depends on the nature and concentration of the dis- 

 solved substances and on the nature of the partition. Under these condi- 

 tions any sudden increase of permeability — sufficient to abolish semi- 

 permeability — must have the same effect as if the partition were sud- 

 denly to disappear; the potential difference between the two solutions 

 then falls to what it would be if no partition separated them. The varia- 

 tion in the electrical potential of the cell-surface during stimulation has 

 in fact the characteristics that we should expect to find if just this 

 change occurs. The electrical variation is always in the direction of an 

 increased negativity of the stimulated region; similarly the dead or in- 

 jured region where the membranes have lost their normal properties 

 always becomes negative, only permanently instead of transitorily so. In 

 stimulation the membrane-change is reversible, in death irreversible. 

 But the direction of the transitory electrical variation of stimulation in- 

 dicates a temporar}' - change in the osmotic properties of the membranes 

 of the same general nature as that associated with death or permanent 

 injury. 



We conclude therefore that during stimulation there occurs a tem- 

 porary and well-marked increase in the permeability of the limiting 

 membranes or protoplasmic surface-films; with this change is associated 

 an electrical depolarization. Experiments with the class of substances 

 known as anesthetics confirms this point of view. When present in 



