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 chloride; and at the same time the change in the pigment-containing cells is also prevented. Rapid 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 immediately 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 increase of permeability during stimulation—i. e., lose their semipermeability for a brief time, the exact duration of which varies characteristically for different tissues.
Stimulation appears always to be accompanied by a change in the electrical properties of the irritable elements; and there is every indication 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 separating two electrolyte solutions becomes the seat of an electrical polarization, whose degree depends on the nature and concentration of the dissolved substances and on the nature of the partition. Under these conditions any sudden increase of permeability—sufficient to abolish semipermeability—must have the same effect as if the partition were suddenly to disappear; the potential difference between the two solutions then falls to what it would be if no partition separated them. The variation 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 injured 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 indicates a temporary-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 temporary 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
