These processes again, like some of those already referred to, appear to be a function of the changing permeability of the plasma-membrane. When we take a tissue consisting of a parallel bundle of cells, like a frog's sartorius muscle, cut it across, place one electrode in contact with the normal uninjured surface of the muscle, and the other with its cut surface, and connect the two with a galvanometer, we find that an electrical current passes—the so-called demarcation-current. The exposed interior (or cut surface) of the cells always shows a lower potential than the exterior; the potential-difference lies usually between a tenth and a twentieth of a volt. This potential-difference depends on the living condition of the cells. It is absent or insignificant in dead muscle. It diminishes when the muscle-surface is treated with cytolytic substances—i. e., with substances which increase the permeability of the plasma-membrane. The evidence, in fact, indicates that the existence of a normal demarcation-current potential is dependent on the semi-permeability of the plasma-membrane. When the permeability is artificially increased, the potential-difference is invariably diminished; its degree thus appears to be dependent on the degree of permeability of the membrane; hence its increase on death or under the influence of membranolytic substances. Now during stimulation the demarcation-current potential always undergoes a marked decrease; this is the change known as the negative variation or action-current, which is an inseparable accompaniment of stimulation. Normally, this change is completely reversible, and when stimulation ceases, the original potential-difference is regained. What is significant from the present point of view is that the direction of the electrical variation accompanying stimulation is the same as in that resulting from death or cytolytic action and associated with an increase of permeability. The phenomenon is thus intelligible on the assumption that during stimulation there is a sudden and marked increase in the permeability of the plasma membrane. This permeability increase, with the accompanying electro-motor variation, differs from that associated with death or cytolysis chiefly in being rapidly and completely reversible. Stimulation may, however, be so excessive under some conditions as to lead to irreversible alterations in the membranes, or even to the death of the cell; i. e., the degree of reversibility is limited, and this consideration explains why excessive stimulation is so injurious—it is in effect equivalent to a cytolytic action or any other action where permeability is irreversibly increased.
Why should a change in the permeability of the membrane produce electrical effects of this kind? The phenomenon becomes intelligible when we remember that membranes act by limiting or preventing diffusion, and that they may limit the diffusion of ions—the mobile, electrically charged atoms and atomic groups present in salt solutions—just
