October 15, 1915] 



SCIENCE 



515 



to apply to muscle, nerve, gland cells, and 

 the excitable tissues of plants, as well as to 

 unicellular organisms. We shall see pres- 

 ently how this fact gives a simple explana- 

 tion of the electrical changes associated 

 with the state of activity. 



If, then, the cell membrane is a part of 

 the cell system as a whole, it is not surpris- 

 ing to find that substances can affect pro- 

 foundly, although reversibly, the activities 

 of the cell, even when they are unable to 

 pass beyond the outer surface. The state 

 of dynamic equilibrium between the cell 

 membrane and the rest of the cell system is 

 naturally affected by such means, since the 

 changes in the one component involve com- 

 pensating ones in the other. Interesting 

 examples of such actions are numerous. I 

 may mention the effect of calcium ions on 

 the heart muscle, the effect of sodium hy- 

 droxide on oxidation in the eggs of the 

 sea-urchin, and that of acids on the con- 

 traction of the jelly-fish. Somewhat puz- 

 zling are those cases in which drugs, such 

 as pilocarpine and muscarine, act only dur- 

 ing their passage through the membrane 

 and lose their effect when their concentra- 

 tion has become equal inside and outside 

 the ceU. 



The work of Dale on anaphylaxis leads 

 him to the conclusion that the phenomena 

 shown by sensitized plain muscle can most 

 reasonably be explained by colloidal inter- 

 action on the surface of the fibers. The 

 result of this is increased permeability and 

 excitation resulting therefrom. 



I referred previously to the electrical 

 change in excitable tissues and its relation 

 to the cell membrane. It was, I believe, 

 first pointed out by Ostwald and confirmed 

 by many subsequent investigators, that in 

 order that a membrane may be imperme- 

 able to a salt it is not a necessary condi- 

 tion that it shall be impermeable to both the 

 ions into which this salt is eleetrolytically 



dissociated. If impermeable to one only of 

 these ions, the other, diffusible, ion can not 

 pass out beyond the point at which the os- 

 motic pressure due to its kinetic energy bal- 

 ances the electrostatic attraction of the op- 

 positely charged ion, which is imprisoned. 

 There is a Helmholtz double layer formed 

 at the membrane, the outside having a 

 charge of the sign of the diffusible ions, the 

 inside that of the other ions. Now, suppose 

 that we lead off from two places on the sur- 

 face of a cell having a membrane with such 

 properties to some instrument capable of 

 detecting differences of electrical potential. 

 It will be clear that we shall obtain no in- 

 dication of the presence of the electrical 

 charge, because the two points are equi- 

 potential, and we can not get at the inte- 

 rior of the cell without destroying its struc- 

 ture. But if excitation means increased 

 permeability, the double layer will disap- 

 pear at an excited spot owing to indiscrimi- 

 nate mixing of both kinds of ions, and we 

 are then practically leading off from the 

 interior of the cell, that is, from the inter- 

 nal component of the double layer, while 

 the unexcited spot is still led off from the 

 outer component. The two contacts are no 

 longer equipotential. Since we find experi- 

 mentally that a point at rest is electrically 

 positive to an excited one, the outer compo- 

 nent must be positive, or the membrane is 

 permeable to certain cations, impermeable 

 to the corresponding anions. Any action 

 on the cell such as would make the mem- 

 brane permeable, injury, certain chemical 

 agents, and so on, would have the same 

 effect as the state of excitation. If we may 

 assume the possibility of degrees of perme- 

 ability, the state of inhibition might be pro- 

 duced by decrease of permeability of the 

 membrane of a cell, which was previously 

 in a state of excitation owing to some influ- 

 ence inherent in the cell itself or coming 

 from the outside. This manner of account- 



